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Cell Rep DOI:10.1016/j.celrep.2014.03.035

Functional genomic analysis of human mitochondrial RNA processing.

Publication TypeJournal Article
Year of Publication2014
AuthorsWolf, AR, Mootha, VK
JournalCell Rep
Date Published2014 May 08
KeywordsCell Line, DNA, Mitochondrial, Genomics, HEK293 Cells, Humans, Mitochondria, Mitochondrial Diseases, Neoplasm Proteins, RNA, RNA Interference, RNA Processing, Post-Transcriptional, RNA, Small Interfering, RNA-Binding Proteins

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.


Alternate JournalCell Rep
PubMed ID24746820
PubMed Central IDPMC4289146
Grant ListR01 GM077465 / GM / NIGMS NIH HHS / United States
GM077465 / GM / NIGMS NIH HHS / United States