epigenetics: rnai and heterochromatin formation. rnai pathways rnai (rna interference) ->...
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Epigenetics:RNAi and Heterochromatin formation
RNAi pathways
• RNAi (RNA interference) -> silencing by dsRNA• dsRNA -> siRNA -> target mRNA ->
PostTranscriptional Gene Silencing (PTGS)• dsRNA -> siRNA -> target chromatin ->
Transcriptional Gene Silencing (TGS)• Dicer: RNase III class ribonuclease -> convert
dsRNA -> siRNA• Argonaute/PIWI family: RNAse H -> cleaving
target mRNA
Three main RNAi complexes
1 RISC (RNA-Induced Silencing Complex): siRNA,Argonaute, -> remove target mRNAs (PTGS)
2 RITS (RNA-Induced Transcriptional Silencing Complex): siRNA, target chromatins (TGS)
3 miRNA-mediated silencing mechanism: endogenous non-coding gene -> miRNA by Dicer and Argonaute -> suppress translation
Sources of dsRNA
Early indications
• PSTV (potato spindle tuber viroid): a 359-nt RNA virus triggers DNA methylation on any transgenic PSTV sequences in the host genome, and this requires the viroid transcription
• In plants, aberrant transcripts trigger DNA methylation of similar sequences
Connection of RNAi with Heterochromatin formation
Mutations in RNAi complex (dcr1, ago1, rdp1) in S. pombe caused loss of heterochromatin and accumulation of repeat-derived transcripts
Sequencing of a small RNA library (~22 nt long) derived many hit from centromeric repeats
dsRNA and siRNA generation
• Bi-directional transcription of repeats• Transcription of inverted repeats• In S. pombe, RDRC (RNA-directed RNA
polymerase Complex) is required for siRNA production: Rdp1, Cid12, Hrr1
Conservation of RNAi and Heterochromatin assembly proteins
siRNA target via RNA-RNA models
Two models for targeting RITSRNA-DNA modelVsRNA-RNA model
Disturbance in transcription causes failure in PTGS
Localizing RITS complex to centromeric regions, which is also siRNA dependent
RNAi-mediated Chromatin and DNA modification in Arabidopsis
RNA-directed RNA polymerases(RdRP, RdR2, RNA POL IV)
siRNA production by DCL3
H3K9 methylation (KYP/SUVH4)
Chromatin remodeling (DDM1)
DNA methylation (CMT3, MET1,DRM1/2)
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