RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA –...

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RNA silencing Jennifer Grier 1 November 2012

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Transcript of RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA –...

Page 1: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

RNA silencing

Jennifer Grier1 November 2012

Page 2: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Overview

• Timing• Mechanisms• Long non-coding RNA– Xist– Air– HOTAIR

• Short non-coding RNA– siRNA– miRNA– piRNA

Page 3: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Timing/Location of RNA silencing

Nucleus• CDGS: chromatin-dependent gene silencing– TGS: Transcriptional gene silencing– CTGS: Co-transcriptional gene silencing

Cytoplasm• PTGS: post-transcriptional gene silencing

Page 4: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of RNA silencing

• Heterochromatin Formation – TGS, CTGS

• Enhancer - repression of silencing

• Transcript degradation– PTGS

• Translational arrest – PTGS

Page 5: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of RNA silencing

• Heterochromatin Formation – TGS, CTGS

Adapted from: Kevin V. Morris. Oligonucleotides. 2009 December;19(4):299-305.

Page 6: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of RNA silencing

• Heterochromatin Formation – TGS, CTGS

• Enhancer - repression of silencing

XX

XAdapted from: Kevin V. Morris. Oligonucleotides. 2009 December;19(4):299-305.

Page 7: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of RNA silencing

• Transcript degradation– PTGS

• Translational arrest – PTGS

Moazed, D. Nature. 2009 Jan 22;457(7228):413-20.

(arrest)

http://proxy.library.upenn.edu:2082/pubmed/19158787
Page 8: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Long non-coding RNA’s

Abbreviated as lncRNA,or lincRNA (long intergenic non-coding RNA)

• Defined as:– >200 bp in length (can be up to 100 kb)– Not processed – Non-protein coding

• Very prevalent in genome

Page 9: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mercer et al., NRG 2009

Found in many places in the genome

lncRNAGene transcript

Page 10: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How do they work?• chromatin regulator recruitment

Mercer et al., NRG 2009

Page 11: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How do they work?• chromatin regulator recruitment• RNA binding protein recruitment

RNA binding protein inhibits HATs

Mercer et al., NRG 2009

Page 12: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How do they work?• chromatin regulator recruitment• RNA binding protein recruitment• TF recruitment/nuclear import

Mercer et al., NRG 2009

Enhancer RNA

Some lncRNA in HOX cluster interact with Trithorx resulting in H3K4me3

Page 13: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How do they work?• chromatin regulator recruitment• RNA binding protein recruitment• TF recruitment (triple helix)• interference with binding or activity of the general transcriptional machinery

Mercer et al., NRG 2009

Page 14: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Koziol and Rinn COGD, 2010

Mechanisms of Chromatin Regulation

Important to note:

Cis or Trans

Page 15: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of Chromatin Regulation

Koziol and Rinn COGD, 2010

• Tethers: sequence specificity

Page 16: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of Chromatin Regulation

Koziol and Rinn COGD, 2010

• Tethers: sequence specificity

• Acts as Scaffold

Page 17: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of Chromatin Regulation

Koziol and Rinn COGD, 2010

• Tethers: sequence specificity

• Acts as Scaffold

• Regulates activity

Page 18: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of Chromatin Regulation

Koziol and Rinn COGD, 2010

• Tethers: sequence specificity

• Acts as Scaffold

• Regulates activity

• Mediates long range interactions

Page 19: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Mechanisms of Chromatin Regulation

• Tethers: sequence specificity

• Acts as Scaffold

• Regulates activity

• Mediates long range interactions

Means of carrying epigenetic information from mother to daughter cell

Page 20: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

X inactivation

Pontier, DB and Gribnau, J. Hum Genet. 2011 August; 130(2): 223–236.

FISH = fluorescent in situ hybridization

polycomb

Page 21: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Magenta: Jpx RNA, green XISTTian et al. Cell 2010

X inactivation: additional players

X-inactivation center4 ncRNAs• Xi : Xist and RepA– RepA binds PRC2

• Xa: Tsix• cis-Xist repressor

• Both: Jpx • cis- and trans-Xist

activator

Page 22: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Xist only expressed in heterochromatinRepA stem loop binds PRC2 – leading to H3K27me3 in cis on XiAllows activation by JPX

Caley et al., The Scientific World Journal 2010

X inactivation: additional playersTsix recruits Dnmt3a– Methylates Xist promoterActivation by JPX is blocked

Page 23: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Ideraabdullah, Mut. Res., 2008

AIR recruits G9a (HMT)

Results in H3K9me at imprinted gene promoters in cis

Igf2r/Air - lncRNA mediated imprinting

Page 24: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

HOTAIR

Gupta et al. Nature 2101

• Expressed from HOXC locus

• Represses in trans

Developmentally regulated (Hox genes)

Page 25: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Tsai et al., Science 2010

HOTAIR

• Binds: – PRC2– EZH2 (HMT)– CoREST

(HDAC)– LSD1

(H3K4me demethlase)

Page 26: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Moazed Nature 2009

(RNAi)

Small non-coding RNAs

Page 27: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

RNAi = RNA-interference

Double stranded (ds) RNA induces homology-dependent degradation of cognate RNA and depletion of protein over time

Page 28: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Andrew Z. Fire Craig C. Mello1/2 of the prize 1/2 of the prizeUSA USAStanford University University of MassachusettsSchool of Medicine Medical SchoolStanford, CA, USA Worcester, MA, USA

The Nobel Prize in Physiology or Medicine 2006"for their discovery of RNA interference - gene silencing by double-stranded RNA"

Page 29: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Functions:

viral silencing in plants

suppression of transposable elements

silencing of repetitive sequences

heterochromatin formation

transgene silencing

Small interfering RNAs: siRNAs

Page 30: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Source for siRNA:

Endogenous

Exogenous

Page 31: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How are small ncRNA generated?

• siRNA– natural cis antisense siRNAs

– repeat associated siRNA

• Result in dsRNA products

• PolII/V transcribed or bi-directional transcription

Moazed Nature 2009

Page 32: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Moazed Nature 2009

How are small ncRNA generated?

• From aberrant transcripts• By RdRp: RNA-dependent RNA polymerase

Page 33: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

How are small ncRNA generated?

• miRNA– from miRNA genes (non-coding)– found within lncRNAs and coding genes– PolII transcribed– Forms a hairpin

Page 34: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Tamari and ZamorePrespectives: machines for RNAiGenes &Dev.19:517-529 (2005)

Processing of small ncRNAs

Page 35: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Processing of miRNAs

Page 36: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

DCL Arabidopsisinitially isolated as developmental mutant!

Dicer Ribonuclease III homolog; helicaseDrosophila, C.elegans, mouse, fungi

Role for a bidentate ribonuclease in the initiation step of RNA interferenceEmily Bernstein, Amy A. Caudy, Scott M. Hammond & Gregory J. Hannon

NATURE | VOL 409 | 18 JANUARY 2001

Processing of miRNAs

Page 37: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Binds precursor ds or miRNA through PAZ domainCleaves precursor through ribonuclease III domainSpacing between PAZ and RIII domains determine size and cut location resulting in staggered cuts

Moazed Nature 2009

Processing of miRNAs

Page 38: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Functions of small ncRNA

Page 39: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

• Argonaute family of proteins– bind miRNA or siRNA

or piRNA• At least two classes– AGO-like– PIWI-like

Important Components

Page 40: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Important Components

• AGO (Argonaute)• PIWI domain binds 5’ end small RNA (RNAse H-like fold)• PAZ domain binds 3’ end small RNA guide strand• Mid domain binds CAP

• Slicer activity (some AGOs)required for siRNA, most plant miRNAmakes a cut in target RNA leading to degradation

• Catalytically inactive AGOs lead to inhibition of translation (stalling)

• Multi turnover enzyme

Page 41: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

RNA-directed RNA polymerase RdRP:

AmplificationTransport (systemic RNAi)Heterochromatin formation

Not required for Drosophila or mammalian RNAi

Important Components

Moazed Nature 2009

Page 42: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

RITS complex

RNA induced transcriptional silencingAgo1 (Argonaute, binds siRNAs)Chp1 (chromodomain, binds H3K9me)Tas3 (binds Ago1 and Chp1, spreading)siRNAs (small inhibitory RNA)

Like RISC: effector complex, bind small RNA

Important Components

Page 43: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Transcriptional Gene Silencing

Djupedal and Ekwall, Cell Research, 2009

Page 44: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Transcriptional Gene Silencing

Djupedal and Ekwall, Cell Research, 2009

Page 45: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Transcriptional Gene Silencing

Djupedal and Ekwall, Cell Research, 2009

Page 46: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

initiation

amplification

de novo DNA methylationSimon and Meyers COPB 2011

RNA induced DNA Methylation

-- Role of siRNAs in ESTABLISHMENT of transcriptional gene

-- silencing first discovered in plants

RNA methods of TGS

Page 47: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

tasiRNAs

Djupedal and Ekwall, Cell Research, 2009

, V

PolIV and V in TGS

Page 48: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PolIV and V in TGSPolIV

PolV

Wierzbicki et al. Cell, 2008

Page 49: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Wierzbicki et al. Cell, 2008

PolIV and V in TGS

Page 50: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Wierzbicki et al. Cell, 2008

PolIV and V in TGS

Page 51: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Haag and Pikaard, Nat. Rev. MCB, 2011

RNA methods of TGS (in plants)

Page 52: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Maintenance

spreading

RNA methods of TGS (in plants)

Page 53: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

TGS speading A. thaliana

RNA methods of TGS (in plants)

Page 54: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Khraiwesh et al., Cell 2010

High levels of miRNA:

Cause miRNA:mRNA duplex formation

Trigger DNA methylation

(for example in response to hormone treatment)

Also described in mammalsKim et al, PNAS 2008

In moss: role of miRNA in DNA methylation

RNA methods of TGS (in plants)

Page 55: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Role of siRNAs in silencing (plants)

triggers DNA methylation

recruitment of H3K9me

role in maintenance of DNA methylation

spreading

Page 56: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Lejeune and Allshire, COCB 2011

RNA methods of TGS (S. pombe)

Page 57: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Role of siRNAs in silencing (S. pombe)

initiation of all heterochromatintogether with Clr4 (HMT)!

maintentance of centromeric heterochromatin

tethered via RITS, Clr4-dependent

RITS brings in nascent transcript

RNA methods of TGS (S. pombe)

Page 58: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Potential for Inheritance?

1.siRNAs inherited, trigger H3K9me

2.Positive feedback between siRNAs and H3K9me: amplification and stabilization

YES!

Page 59: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

piRNAFound in animalsRole in germline

Silencing of of repetitive DNAtransposons, subtelomeric regionspericentromeric regions

PROTECTING THE GERMLINE

Page 60: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PIWI: role in piRNA generation

Moazed Nature 2009

PROTECTING THE GERMLINE

Page 61: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

piRNA

2ndary piRNA

Dicer independent

PIWI-AGO

example of AGO activity

Page 62: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PIWI associates with HP1

D.m. piRNAs from follicle cells into oocytes

also linked to triggering DNA methylation

Accumulate at time of erasure and re-establishment of DNA methylation

PROTECTING THE GERMLINE

Page 63: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Slotkin et al., Cell 2009

Similar observations for female gametophyte

PROTECTING THE GERMLINE

Page 64: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

In mammals: TE silencing via DNA methylation

pericentromeric RNA involved

Occurs early after fertilization

Satenard et al. Nat. Cell. Biol. 2010Probst et al. Dev Cell 2010

PROTECTING THE GERMLINE

Page 65: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

AGO-linked activities

Transcriptional Gene Silencing

Page 66: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PolIV

PolII

TGS

PTGS (post transcriptional gene silencing)message cleavage inhibition of translation

(small and large ncRNAs)

Page 67: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PTGSsiRNA

Page 68: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

PTGS

• RISC complex RNA-induced silencing complex

• si RNA– AGO– DCR– dsRNA binding protein (TRBP)

• miRNA– AGO– GW182

Page 69: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

FEBS letters 2005

PTGS

Page 70: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Small ncRNA movement

some miRNAs can move (short distance)

siRNAs can move: systemic responses

Systemic Silencing

Page 71: RNA silencing Jennifer Grier 1 November 2012. Overview Timing Mechanisms Long non-coding RNA – Xist – Air – HOTAIR Short non-coding RNA – siRNA – miRNA.

Summarytypes of long noncoding RNAs

definition, where arise

roles of lnc RNAs in chromatin regulation

types of small noncoding RNAsdefinition, biogenesis

roles in chromatin regulation initiation and maintenance

Potential for epigenetic inheritance

Role in germline

Systemic silencing: why important?


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