Structure of the nuclease subunit of human mitochondrial RNase P

Mitochondrial RNA polymerase produces long polycistronic precursors that contain the mRNAs, rRNAs and tRNAs needed for mitochondrial translation. Mitochondrial RNase P (mt-RNase P) initiates the maturation of the precursors by cleaving at the 5' ends of the tRNAs. Human mt-RNase P is only activ...

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Veröffentlicht in:Nucleic acids research 2015-06, Vol.43 (11), p.5664-5672
Hauptverfasser: Reinhard, Linda, Sridhara, Sagar, Hällberg, B Martin
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Sprache:eng
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Zusammenfassung:Mitochondrial RNA polymerase produces long polycistronic precursors that contain the mRNAs, rRNAs and tRNAs needed for mitochondrial translation. Mitochondrial RNase P (mt-RNase P) initiates the maturation of the precursors by cleaving at the 5' ends of the tRNAs. Human mt-RNase P is only active as a tripartite complex (mitochondrial RNase P proteins 1-3; MRPP1-3), whereas plant and trypanosomal RNase Ps (PRORPs)-albeit homologous to MRPP3-are active as single proteins. The reason for this discrepancy has so far remained obscure. Here, we present the crystal structure of human MRPP3, which features a remarkably distorted and hence non-productive active site that we propose will switch to a fully productive state only upon association with MRPP1, MRPP2 and pre-tRNA substrate. We suggest a mechanism in which MRPP1 and MRPP2 both deliver the pre-tRNA substrate and activate MRPP3 through an induced-fit process.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkv481