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7/28/2019 Week2_Part6
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Many classes of small, mid-sized and long noncoding RNAs, only someof which we will cover
MicroRNAs (miRNAs) post-transcriptional gene silencing Piwi-interacting RNAs (piRNAs) control transposable elements and
direct DNA methylation at transposable elements
Long non-coding RNAs (lncRNAs) appear todirect epigenetic machinery and establish
different epigenetic states
Non-coding RNAs
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Single stranded precursors transcribed frompiRNA clusters
Primary processing involves shortening Secondary processing - Ping-pong amplification piRNA- PIWI protein complexes allow
1. Degradation of transposon RNA ie. post-transcriptionalsilencing
piRNA biogenesis
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Single stranded precursors transcribed frompiRNA clusters
Primary processing involves shortening Secondary processing - Ping-pong amplification piRNA- PIWI protein complexes allow
1. Degradation of transposon RNA ie. post-transcriptionalsilencing
2. DNA methylation of transposon/ repetitive element DNAi.e. transcriptional silencing via RNA directed DNA
methylation (MIWI2 imported back to the nucleus)
piRNA biogenesis
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piRNAs are important in the germ line and also in stem cells Mice without various Mili1 and Mili2 proteins are sterile due to impaired
spermatogenesis, associated with failure to silence repetitive elements
such as LINE1 and IAP elements Mutations in human PIWI proteins associated with infertility PIWI proteins aberrantly expressed in cancer,
demonstrating their role outside the germ line,
possibly related to stem cells
piRNAs in development and disease
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piRNAs in silencing non-repetitive regions?
piRNAs in pachytene sperm target non-repetitive DNA Active at Rasgrf1 paternally imprinted gene (see later lectures on Imprinting)
piRNAs are involved in directing DNA methylation
at more loci than just transposable elements
Still much to be understood
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