Dataset Information

A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis.

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.

SUBMITTER: Liu X

PROVIDER: S-EPMC4169771 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis.

Liu Xuhang X Zheng Qi Q Vrettos Nicholas N Maragkakis Manolis M Alexiou Panagiotis P Gregory Brian D BD Mourelatos Zissimos Z

Molecular cell 20140828 6

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 ...[more]

PMID: 25175028

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Project description:BackgroundDelivery of high-quality colonoscopy and adherence to evidence-based surveillance guidelines is essential to a high-quality screening program, especially in safety net systems with limited resources. We sought to assess colonoscopy quality and ensure appropriate surveillance in a network of safety net practices.MethodsWe identified age-eligible patients ages 50-75 within a Federally Qualified Health Center (FQHC) clinic system with evidence of colonoscopy in preceding 10 years. We performed chart reviews to assess key aspects of colonoscopy quality: bowel preparation quality, evidence of cecal intubation, cecal withdrawal time, and the adenoma detection rate. We then utilized established guidelines to assess and revise surveillance colonoscopy intervals, determine whether appropriate surveillance had taken place, and schedule overdue patients as appropriate.ResultsOf 26,394 age-eligible patients, a total of 3,970 patients had evidence of prior colonoscopy and 1,709 charts were selected and reviewed. Mean age was 57, 54% identified as women and 51% identified as Hispanic. Of 1709 colonoscopies reviewed, 77% had data on bowel preparation, and of those, 85% had adequate preparation quality. Cecal intubation was documented in 89% of procedures. Adequate cecal withdrawal time was documented in 59% of those with documented cecal intubation. Overall adenoma detection rate was 42%. Initial surveillance interval was clearly stated in 72% (n = 1238) of procedures. Of these, initial recommended intervals were too short in 24.5% (n = 304) and too long in 3.6% (n = 45). A total of 132 patients (10.7%) were overdue for appropriate surveillance and were referred for follow-up colonoscopy.ConclusionsOverall, the quality of screening colonoscopy was high, but reporting was incomplete. We found fair adherence to evidence-based surveillance guidelines, with significant opportunities to extend surveillance intervals and improve adherence to best practices.

Dataset Information

A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis.

Publications

A MicroRNA precursor surveillance system in quality control of MicroRNA synthesis.

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