Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative...
Transcript of Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative...
![Page 1: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/1.jpg)
Udział metabolizmu RNA
w procesach fizjologicznych:
rozwój i odpowiedź na stres
Anna Golisz
![Page 2: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/2.jpg)
Levels of regulation
I. Chromatin and transcription
II. RNA processing: pre-mRNA splicing
(alternative splicing - AS) and 3’ formation
III. RNA stability
IV.Regulation via microRNA
![Page 3: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/3.jpg)
RNA metabolism regulates most of developmental and
signaling processes in plants
► Germination
► Circadian clock
► Transition from vegetative to
generative development
► Flowering
► Stress response
Regulation of plant metabolism
I. Chromatin and transcription
![Page 4: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/4.jpg)
Plant clocks control a plethora of biological processes
2000, vol. 5, no. 12
![Page 5: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/5.jpg)
The central oscillator
1) CCA1 – CIRCADIAN CLOCK ASSOCIATED 1
LHY – LATE ELONGATED HYPOCOTYL
MYB transcription factors
reduction in mRNA levels: negative feedback loop
mRNA level peaking at dawn
2) TOC1 – TIMING OF CAB EXPRESSION 1
TOC1 expression oscillates peaking
during early evening
(opposite to CCA1 and LHY)
Stratmann & Mas, Seminars in Cell & Developmental Biology (2008) 554–559
![Page 6: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/6.jpg)
Chromatin-dependent regulation of TOC1
Stratmann & Mas, Seminars in Cell & Developmental Biology 19 (2008) 554–559
HAT – histone acetyltransferase
HDAC – histone deacetylase
![Page 7: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/7.jpg)
Model for a feedback loop involving
LHY, CCA1 and TOC1
3) LHY, CCA1 repress expression of TOC1,
their positive regulator
1) PHY and CRY as photoreceptors
2) LHY, CCA1 and TOC1 negative
feedback loop
4) Generation of circadian rhythms, including
that of CO (CONSTANTS) for flowering time
5) ELF3 (early flowering3) gates the light signals,
resetting it at dawn
6) ZTL (ZEITLUPE) and GI (GIGANTEA) also act
on light input
FT – FLOWERING LOCUS T 2003, 6:13-19
![Page 8: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/8.jpg)
Flowering
pathway in plant
Flowering
I-II.
Chromatin
and RNA
processing
![Page 9: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/9.jpg)
Pathways controlling flowering time in A. thaliana
Int. J. Dev. Biol. 2005, 49: 773-780
![Page 10: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/10.jpg)
Functions of antisense RNAs in the regulation of
plant flowering
Rosonina and Manley, Dev. Cell, 2010
Hornyik et al.. RNA UK, 2010
FLC – Flowering Locus C
− MADS box transcription
factor
− major repressor of
flowering in plants
− expression regulated by
FLC antisense
► two major forms of FLC antisense are synthesized
► regulated by alternative polyadenylation by RNA binding proteins, FPA
and FCA, and CTSF factor FY
► short asFLC (3’ processing at site I) recruits histone demethylase FLD which
introduces transcriptionally repressive histone modifications leading to
FLC silencing
► long asFLC (3’ processing at site II) causes nucleosomal rearrangements at
the FLC promoter leading to FLC transcription
![Page 11: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/11.jpg)
Convergence points in abiotic and biotic stress signaling networks
Fujita et al. Current Opinion in Plant Biology 2006, 9:436–442
I and III. Transcription and RNA stability
Stress response
![Page 12: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/12.jpg)
Phytohormones – old timers and newcomers
Auxin
Cytokinin Gibberellin
Abscisic Acid
Ethylene
Brassinosteroid Salicylic
Acid
Jasmonic Acid
Strigolactone
![Page 13: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/13.jpg)
Phytohormones regulate all stages of the
plant life cycle
Fertilization and
fruit formation
Seed
dormancy Embryogenesis
Fruit
ripening
Germination
Flower
development
Growth and
branching
![Page 14: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/14.jpg)
Hormonal responses to abiotic stress
Photooxidative
stress
High temperature
stress
Water deficit,
drought
Soil salinity
Air pollution
Wounding and
mechanical damage
Cold and
freezing stress
Plants’ lives are
very stressful...
ABA and
ethylene help
plants respond
to stress
Reprinted by permission from Macmillan Publishers, Ltd. Nature Chemical Biology. Vickers, C.E.,
Gershenzon, J., Lerdau, M.T., and Loreto, F. (2009) Nature Chemical Biology 5: 283 - 291
![Page 15: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/15.jpg)
Adapted with permission from RIKEN
Seed quality
Stress tolerance
Dormancy Germination
Biotic stress
response
Stomatal aperture Gene expression
Development Abscisic Acid
controls many plant processes including stress responses,
development and reproduction
ABSCISIC ACID (ABA)
![Page 16: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/16.jpg)
ABA synthesis is strongly induced in
response to stress
R.L. Croissant, , Bugwood. www.forestryimages.org . Zabadel, T. J. Plant Physiol. (1974) 53: 125-127.
ABA levels rise during drought stress
due in part to increased biosynthesis
Hours of drought stress
Leaf
water
potential
(atm)
[ABA]
µg/g dry
weight
![Page 17: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/17.jpg)
Abscisic acid (ABA) signaling pathway
Sheard and Zheng NATURE Vol 462/3 December 2009
![Page 18: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/18.jpg)
There are many genes encoding
PYR/PYL/RCARs
Common Name Species Number of genes
Soybean Glycine max 23
Corn Zea mays 20
Western poplar Populus trichocarpa
14
Rice Oryza sativa 11
Grape Vitis vinifera 8
Sorghum Sorghum bicolor 8
Barrel medic (a model legume)
Medicago truncatula
6
Arabidopsis Arabidopsis thaliana
14
Klingler, J.P., Batelli, G., and Zhu, J.-K. J. Exp.Bot. 61: 3199-3210
Raghavendra, A.S., Gonugunta, V.K., Christmann, A., and Grill, E. (2010) Trends Plant Sci. 15: 395-401.
The 14 PYR/RCARs in Arabidopsis
![Page 19: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/19.jpg)
Schematic model of the transcriptional regulation
of ABA signaling by AREB/ABF and ABI5 family TFs
Fujita et al. 2011 J Plant Res
![Page 20: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/20.jpg)
ahg2-1 – ABA hypersensitive germination
poly(A)-specific ribonuclease AtPARN
deadenylation, mRNA degradation
lba1 – ABA-hypersensitive seed germination
RNA helicase UPF1 Nonsense-Mediated decay (NMD)
Nonsense-Mediated mRNA decay
sad1 – supersensitive to ABA and drought
LSM complex (Sm-like) snRNP proteins
mRNA splicing and degradation
ABA response in RNA metabolic mutants
hyl1 – hypersensitive to salt and ABA
RNA binding protein HYL1
miRNA processing and accumulation
los4 – sensitive to ABA and cold
putative DEAD box RNA helicase LOS4
mRNA export
m7G
Lsm1-7
m7G
PARN
abh1 – hypersensitive response to ABA in germination inhibition
nuclear cap-binding protein CBP80
mRNA splicing and stability
![Page 21: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/21.jpg)
ABA response
involves RNA
processing and
degradation
systems
Hirayama&Shinozaki 2007
TRENDS in Plant Science
![Page 22: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/22.jpg)
Ethylene (C2H4) is a gaseous hormone
with diverse actions
Ethylene regulates:
fruit ripening
organ expansion
senescence
gene expression
stress responses
Cotton plants
7 days ethylene Air (control)
Air Ethylene
Arabidopsis
Beyer, Jr., E.M. (1976) Plant Physiol. 58: 268-271.
![Page 23: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/23.jpg)
Ethylene responses in Arabidopsis
Lorenzo, O., Piqueras, R., Sanchez-Serrano, J.J., and Solano, R. (2003). Plant Cell 15: 165-178;
Rüžička, K., Ljung, K., Vanneste, S., Podhorská, R., Beeckman, T., Friml, J., and Benková, E. (2007). Plant Cell 19: 2197-2212.
Inhibition of leaf
cell expansion Acceleration of leaf senescence
Ethylene-induced gene expression
Inhibition of root
elongation
![Page 24: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/24.jpg)
=XRN4
Ethylene signal transduction pathway:
XRN4 - 5’-3’ cytoplasmic exoribonuclease
Olmedo et al. PNAS 2006 vol. 103 no. 36
![Page 25: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/25.jpg)
miRNAs and vegetative phase change
Germination
zygote
JUVENILE
PHASE
Vegetative phase
change
Vegetative phase change is the transition from juvenile
to adult growth in plants
ADULT
PHASE
REPRODUCTIVE
PHASE
EMBRYONIC
PHASE
IV. Regulation via miRNA
![Page 26: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/26.jpg)
►Small RNAs are a pool of 21 to 24 nt
RNAs that generally function in gene
silencing
►Small RNAs contribute to post-
transcriptional gene silencing by
affecting mRNA translation or stability
►Small RNAs contribute to
transcriptional gene silencing through
epigenetic modifications to chromatin
AAAAA
RNA Pol
Histone modification, DNA methylation
What are small RNAs?
![Page 27: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/27.jpg)
Leaves are modulated by miRNA activity
throughout development
Pulido, A., and Laufs, P. (2010). J.Exp.Bot. 61: 1277-1291
![Page 28: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/28.jpg)
M.W. Jones-Rhoades et al. Annu. Rev. Plant Biol. 2006. 57:19–53
Phenotypes resulting from microRNA (miRNA)
overexpression in Arabidopsis
miRNA156
miRNA164
miRNA172
miRNA319
miRNA166
miRNA159a
miRNA160
![Page 29: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/29.jpg)
Phase change is specified by miRNAs HASTY, with a shortened juvenile phase,
encodes a protein needed for miRNA
export from nucleus to cytoplasm
hasty
Loss-of-function zippy
mutants prematurely express
adult vegetative traits. ZIPPY
encodes an ARGONAUTE
protein, AGO7
Wild-type
zippy
Bollman, et al. (2003) Development 130: 1493-1504
Hunter et al. (2003) Curr. Biol. 13: 1734–1739
WT hasty
WT zippy
![Page 30: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/30.jpg)
Poethig, R.S. (2009) Curr. Opin. Genet. Devel.
miR156 overexpression prolongs juvenile
phase in Arabidopsis
![Page 31: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/31.jpg)
Reciprocal expression patterns of
MIR156 and MIR172 in the juvenile and adult
phase of development
Chuck et al. Current Opinion in Plant Biology 2009, 12:81–86
![Page 32: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/32.jpg)
miR172 expression temporally regulates
AP2-like proteins
It is thought that
floral initiation can
occur when the
level of AP2-like
floral inhibitors
drops below a
certain level
Aukerman, M.J., and Sakai, H. (2003) Regulation of flowering time and floral organ identity by a microRNA and its APETALA2-Like target genes Plant Cell 15: 2730-2741.
WT mutant
ap2-12
![Page 33: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/33.jpg)
Role of conserved plant miRNAs
Khraiwesh et al. 2011 Biochimica et Biophysica Acta
![Page 34: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/34.jpg)
Regulation of miRNA and their target genes by
ABA and salt stress in Arabidopsis
Plant Mol Biol (2009) 71:51–59
The Plant Journal (2007) 49, 592–606
![Page 35: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/35.jpg)
Khraiwesh et al. 2011 Biochimica et Biophysica Acta
green boxes – upregulated small RNA,
light green boxes – slightly upregulated small RNA
red boxes – downregulated small RNA
Stress-regulated small RNAs and their target families
![Page 36: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/36.jpg)
Regulatory network of stress-responsive miRNAs in Arabidopsis
B. Khraiwesh et al. Biochimica et Biophysica Acta 1819 (2012) 137–148
![Page 37: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/37.jpg)
Distinctions between animal and plant
miRNAs
Animal miRNAs Plant miRNAs
conserved miRNA precursors less conserved mature miRNA
pri-miRNA cleaved by DICER
produce 60-70 nt pre-miRNA
pri-miRNA cleaved by Dicer-like1
(DCL1) produce 60-300 nt
miRNA precursor
cleaved to miRNA duplex in the
cytoplasm
cleaved to miRNA duplex in the
nucleus
miRNA duplex is exported from
the nucleus by Exportin-5
miRNA duplex is exported from
the nucleus by HASTY (HST)
homolog Exportin-5
Lu & Huang BBRC 2008, 368, 458-462
![Page 38: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/38.jpg)
Wienholds, Plasterk FEBS Letters 579 (2005) 5911–5922
Biological function of miRNAs in animal and disease
![Page 39: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/39.jpg)
miRNA – control of differentation and
development of mammalian cells
Neuronal
differentiation Muscle cell
differentation
Cell
development
Stefani G., Slack F. J., (2008) Mol Cell Biol
![Page 40: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/40.jpg)
miRNAs regulate developmental timing
miRNAs were discovered
in studies of developmental
progressions in the
nematode C. elegans.
A miRNA encoded by lin-4
is required for proper larval
development.
lin-14 gene
3’ untranslated region
lin-4 binding sites
Lee, R.C., Feinbaum, R.L., and Ambrose, V. (1993). Cell 75: 843–845.
Wightman, B., Ha, I., and Ruvkun, G. (1993). Cell 75: 855–862.
lin-14 mRNA
lin-4 miRNA
![Page 41: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/41.jpg)
Downregulation of lin-14 by lin-4 is
necessary for normal development
Wild-type C. elegans
lin-4 Loss-of-function lin-4 is a negative
regulator of lin-14
In wild-type worms,
lin-14 is expressed
early and then shut
off.
lin-14
expression
lin-4 loss-of-
function
causes lin-14
expression to
remain high.
Lee, R.C., Feinbaum, R.L., and Ambrose, V. (1993). Cell 75: 843–845.
Wightman, B., Ha, I., and Ruvkun, G. (1993). Cell 75: 855–862.
![Page 42: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/42.jpg)
CurrentOpinioninGenetics&Development 2011, 21:491–497
Regulation of dendritic spine
morphogenesis by microRNAs
miR-134 and miR-138 – reduced dendritic spine volume
miR-132 – increased dendritic spine density
miR-125 – decreased dendritic spine width and increased length
![Page 43: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/43.jpg)
► Several miRNAs
(miR183/96/182, miR204, miR211)
are transcriptionally
upregulated by light in
mouse retinal neurons
► Glutamate transporter
SLC1A1 (voltage-dependent) is
one of the targets of the light-
regulated miRNAs
► miRNAs in retinal neurons
decay much faster than in
nonneuronal cells
► Blocking action potentials
or glutamate receptors
strongly affects miRNA
turnover
Light-Regulated Retinal MicroRNAs
Filipowicz et al. Cell 2010, 141, 618-631
microRNA metabolism in neurons is higher than in most other cells types
![Page 44: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/44.jpg)
miRNA as a DECOY in myeloid cell differentiation
Beitzinger and Meister, Cell, 2010
► RNA binding protein hnRNP E2 (activated by BCR/ABL kinase in chronic
myeloid leukemia patients-CML) inhibits
translation of C/EBP mRNA by binding
to its 5’ UTR. This stops MD
► miR-328 directly binds hnRNP E2 due
to sequence similarity to the E2 binding
site on C/EBP mRNA
► translation of C/EBP is activated
leading to MD
► C/EBP stimulates miR-328
transcription (positive feedback loop for MD
fine-tuning)
![Page 45: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/45.jpg)
ncRNAs and disease
Prasanth and Spector, GeneDev, 2007
![Page 46: Udział metabolizmu RNA - IGiB...Loss-of-function zippy mutants prematurely express adult vegetative traits. ZIPPY encodes an ARGONAUTE protein, AGO7 Wild-type zippy Bollman, et al.](https://reader035.fdocument.pub/reader035/viewer/2022071404/60f87b49f351594fd531abfc/html5/thumbnails/46.jpg)
Summary
Chromatin and transcription
RNA processing
mRNA stability
microRNA