Antisense Transcripts Delimit Exonucleolytic Activity of the Mitochondrial 3 ' Processome to Generate Guide RNAs

作者：Suematsu Takuma; Zhang Liye; Aphasizheva Inna; Monti Stefano; Huang Lan; Wang Qi; Costello Catherine E; Aphasizhev Ruslan^*

来源：Molecular Cell, 2016, 61(3): 364-378.

DOI：10.1016/j.molcel.2016.01.004

Small, noncoding RNA biogenesis typically involves cleavage of structured precursor by RNase III-like endonucleases. However, guide RNAs (gRNAs) that direct U-insertion/deletion mRNA editing in mitochondria of trypanosomes maintain 5' triphosphate characteristic of the transcription initiation and possess a U-tail indicative of 3' processing and uridylation. Here, we identified a protein complex composed of RET1 TUTase, DSS1 3'-5' exonuclease, and three additional subunits. This complex, termed mitochondrial 3' processome (MPsome), is responsible for primary uridylation of similar to 800 nt gRNA precursors, their processive degradation to amature size of 40-60 nt, and secondary U-tail addition. Both strands of the gRNA gene are transcribed into sense and antisense precursors of similar lengths. Head-to-head hybridization of these transcripts blocks symmetrical 3'-5' degradation at a fixed distance from the double-stranded region. Together, our findings suggest a model in which gRNA is derived from the 5' extremity of a primary molecule by uridylation-induced, antisense transcription-controlled 3'-5' exonucleolytic degradation.

• 出版日期2016-2-4