“欲穷千里目，更上一层楼”(二十八) ——光寿红

欲实时把握表观遗传学研究最新进展和发展趋势，请参加第四届发育和疾病的表观遗传学上海国际研讨会 (2018-09-18 至 2018-09-21 )，并投递墙报摘要。 [原文来自：www.ii77.com]

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光寿红

sguang@ustc.edu.cn   

http://staff.ustc.edu.cn/~sguang/index.html  

中国科学技术大学  教授        

A new layer of rRNA regulation by small interference RNAs and the nuclear RNAi pathway

Ribosome biogenesis drives cell growth and proliferation, but mechanisms that modulate this process remain poorly understood. For a long time, small ribosomal RNA sequences have been widely treated as non-specific degradation products and neglected as garbage sequences. Recently, we identified a new class of antisense ribosomal siRNAs (risiRNAs) that downregulate pre-rRNA through the nuclear RNAi pathway in C. elegans. risiRNAs exhibit sequence characteristics similar to 22G RNA while complement to 18S and 26S rRNA. risiRNAs elicit the translocation of the nuclear Argonaute protein NRDE-3 from the cytoplasm to nucleus and nucleolus, in which the risiRNA/NRDE complex binds to pre-rRNA and silences rRNA expression.

C27F2.4(ceBUD23) is a m7G methyltransferase of 18S rRNA. E02H1.1(ceDIMT1L) is a predicted m6(2)Am6(2)A methyltransferase of 18S rRNA. The processing deficiency of rRNAs resulted in the accumulation of risiRNAs as well. We isolated SUSI-3(RIOK-1) which is similar to human RIOK1 that cleaves 20S to 18S rRNA.

Therefore, we concluded that erroneous rRNAs can trigger risiRNA generation and subsequently turn on the nuclear RNAi-mediated gene silencing pathway to inhibit pre-rRNA expression, which may provide a quality control mechanism to maintain the homeostasis of rRNAs.

To further understand the biological roles of risiRNA, we conducted both forward and reverse genetic screenings to search for more susi mutants. We isolated a number of genes that are broadly conserved from yeast to humans and are involved in pre-rRNA modification and processing. Among them, SUSI-2(ceRRP8) is engages in m1A methylation of 26S rRNA.