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Functional genomic analysis of human mitochondrial RNA processing.

Abstract：

:Both strands of human mtDNA are transcribed in continuous, multigenic units that are cleaved into the mature rRNAs, tRNAs, and mRNAs required for respiratory chain biogenesis. We sought to systematically identify nuclear-encoded proteins that contribute to processing of mtRNAs within the organelle. First, we devised and validated a multiplex MitoString assay that quantitates 27 mature and precursor mtDNA transcripts. Second, we applied MitoString profiling to evaluate the impact of silencing each of 107 mitochondrial-localized, predicted RNA-binding proteins. With the resulting data set, we rediscovered the roles of recently identified RNA-processing enzymes, detected unanticipated roles of known disease genes in RNA processing, and identified new regulatory factors. We demonstrate that one such factor, FASTKD4, modulates the half-lives of a subset of mt-mRNAs and associates with mtRNAs in vivo. MitoString profiling may be useful for diagnosing and deciphering the pathogenesis of mtDNA disorders.

journal_name

Cell Rep

journal_title

Cell reports

authors

Wolf AR,Mootha VK

doi

10.1016/j.celrep.2014.03.035

subject

Has Abstract

pub_date

2014-05-08 00:00:00

pages

918-31

issue

3

issn

2211-1247

pii

S2211-1247(14)00213-7

journal_volume

7

pub_type

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