Auto-inhibitory Mechanism of the Human Mitochondrial RNase P Protein Complex.

Fengzhi Li,Xue Yang,Yuequan Shen,Xiaofen Liu,Weihong Zhou

doi:10.1038/srep09878

Abstract

It is known that tRNAs play an essential role in genetic information transfer from DNA to protein. The maturation of tRNA precursors is performed by the endoribonuclease RNase P, which classically consists of a main RNA segment and accessory proteins. However, the newly identified human mitochondrial RNase P-like protein (MRPP123) complex is unique in that it is composed of three proteins without RNA. Here, we determined the crystal structure of MRPP123 complex subunit 3 (MRPP3), which is thought to carry out the catalytic reaction. A detailed structural analysis in combination with biochemical assays suggests that MRPP3 is in an auto-inhibitory conformation in which metal ions that are essential for catalysis are excluded from the active site. Our results indicate that further regulation is necessary to rearrange the conformation of the active site of MRPP3 and trigger it, thus providing important information to understand the activation of MRPP123.

Highlights

It is known that tRNAs play an essential role in genetic information transfer from DNA to protein
MRPP123 complex subunit 3 (MRPP3) is the third member in the MRPP123 complex, and it possibly acts as the catalytic subunit of MRPP1231,18
MRPP3 is homologous with PRORP1, which exists in the mitochondria and chloroplasts of Arabidopsis thaliana[15]

Summary

Introduction

It is known that tRNAs play an essential role in genetic information transfer from DNA to protein. T RNAs serve as adaptors in translating nucleotide sequences into amino acid sequences and are usually transcribed as pre-tRNAs1–3 To reach their mature functional state, several steps of processing and modification are required[4]. The endoribonuclease RNase P is a metallonuclease that hydrolyzes 59 leader sequences from the pre-tRNA in the presence of Mg21 or other divalent metal ions[2,5]. RNase P exists in almost all forms of life and is composed of RNA plus one or more proteins[6] Among these components, the RNA is the catalytic subunit, and it recognizes the pre-tRNA and hydrolyzes it, resulting in the production of a 59-RNA leader sequence with a 39-OH and a 39-tRNA with a 59 phosphate[1,7]. MRPP3 fails to cleave the 59 sequence www.nature.com/scientificreports of mitochondrial pre-RNA in the absence of MRPP1 and MRPP2, whereas PRORP1 can carry out this cleavage step by itself[18]

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Results

Conclusion