期刊
RNA
卷 25, 期 12, 页码 1646-1660出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.069310.118
关键词
RNase P; PRORP; MRPP; mitochondria; pre-tRNA methylation
资金
- National Institutes of Health [R01 GM117141, R01 GM55387]
- American Heart Association [16PRE29890011]
Human mitochondrial ribonuclease P (mtRNase P) is an essential three-protein complex that catalyzes the 5' end maturation of mitochondrial precursor tRNAs (pre-tRNAs). Mitochondrial RNase P Protein 3 (MRPP3), a protein-only RNase P (PRORP), is the nuclease component of the mtRNase P complex and requires a two-protein S-adenosyl-methionine (SAM)-dependent methyltransferase MRPP1/2 subcomplex to function. Dysfunction of mtRNase P is linked to several human mitochondrial diseases, such as mitochondrial myopathies. Despite its central role in mitochondrial RNA processing, little is known about how the protein subunits of mtRNase P function synergistically. Here, we use purified mtRNase P to demonstrate that mtRNase P recognizes, cleaves, and methylates some, but not all, mitochondrial pre-tRNAs in vitro. Additionally, mtRNase P does not process all mitochondrial pre-tRNAs uniformly, suggesting the possibility that some pre-tRNAs require additional factors to be cleaved in vivo. Consistent with this, we found that addition of the TRMT10C (MRPP1) cofactor SAM enhances the ability of mtRNase P to bind and cleave some mitochondrial pre-tRNAs. Furthermore, the presence of MRPP3 can enhance the methylation activity of MRPP1/2. Taken together, our data demonstrate that the subunits of mtRNase P work together to efficiently recognize, process, and methylate human mitochondrial pre-tRNAs.
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