Antisense Transcripts Delimit Exonucleolytic Activity of the Mitochondrial 3' Processome to Generate Guide RNAs.
Mol Cell, 2016/2/04;61(3):364-378.
Suematsu T[1], Zhang L[2], Aphasizheva I[1], Monti S[2], Huang L[3], Wang Q[4], Costello CE[4], Aphasizhev R[5]
Affiliations
PMID: 26833087DOI: 10.1016/j.molcel.2016.01.004
Impact factor: 19.328
Abstract
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 ∼800 nt gRNA precursors, their processive degradation to a mature 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.
Keywords: RNA decay; RNA editing; TUTase; exonuclease; guide RNA; mitochondria; trypanosoma
MeSH terms
Exoribonucleases; Gene Expression Regulation; Mitochondria; Protozoan Proteins; RNA; RNA Editing; RNA Nucleotidyltransferases; RNA Stability; RNA, Antisense; RNA, Guide, Kinetoplastida; RNA, Mitochondrial; RNA, Protozoan; Time Factors; Trypanosoma brucei brucei; Uracil Nucleotides
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download