Functional Genomic Analysis of Human Mitochondrial RNA Processing

Ashley R. Wolf, Vamsi K. Mootha

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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.

Original languageEnglish
Pages (from-to)918-931
Number of pages14
JournalCell Reports
Volume7
Issue number3
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Dive into the research topics of 'Functional Genomic Analysis of Human Mitochondrial RNA Processing'. Together they form a unique fingerprint.

Cite this