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A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis
- Source :
- Molecular cell. 55(6)
- Publication Year :
- 2013
-
Abstract
- MicroRNAs (miRNAs) are essential for regulation of gene expression. Though numerous miRNAs have been identified by high-throughput sequencing, few precursor miRNAs (pre-miRNAs) are experimentally validated. Here we report a strategy for constructing high-throughput sequencing libraries enriched for full-length pre-miRNAs. We find widespread and extensive uridylation of Argonaute (Ago)-bound pre-miRNAs, which is primarily catalyzed by two terminal uridylyltransferases: TUT7 and TUT4. Uridylation by TUT7/4 not only polishes pre-miRNA 3' ends, but also facilitates their degradation by the exosome, preventing clogging of Ago with defective species. We show that the exosome exploits distinct substrate preferences of DIS3 and RRP6, its two catalytic subunits, to distinguish productive from defective pre-miRNAs. Furthermore, we identify a positive feedback loop formed by the exosome and TUT7/4 in triggering uridylation and degradation of Ago-bound pre-miRNAs. Our study reveals a pre-miRNA surveillance system that comprises TUT7, TUT4, and the exosome in quality control of miRNA synthesis.
- Subjects :
- Genetics
Regulation of gene expression
Genome
Exosome Multienzyme Ribonuclease Complex
HEK 293 cells
MiRNA Synthesis
High-Throughput Nucleotide Sequencing
RNA Nucleotidyltransferases
Computational biology
Cell Biology
Argonaute
Biology
Exosomes
Exosome
Article
MicroRNAs
HEK293 Cells
MicroRNA synthesis
microRNA
Argonaute Proteins
Humans
Molecular Biology
Uridine
Subjects
Details
- ISSN :
- 10974164
- Volume :
- 55
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Molecular cell
- Accession number :
- edsair.doi.dedup.....47500ffd5db84bdb5e66a3e6ab19f297