tRNase Z

Ceballos, María Esther Gutiérrez-Díaz; Vioque, Agustı́n

doi:10.2174/092986607779816050

Cited by 23 publications

(12 citation statements)

References 62 publications

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“…The in vivo rescue of function in mitochondria with mt-tRNA mutations has proven challenging (5). The usual processing of nucleus-encoded tRNA precursors occurs inside the nucleus (34,35). When stably expressed from inside the nucleus, mt-tRNA precursors with the fused RP sequence did not rescue the respiratory defect of MERRF or MELAS cells (Fig.…”

Section: Resultsmentioning

confidence: 95%

Correcting human mitochondrial mutations with targeted RNA import

Wang¹,

Shimada²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

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Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence from the H1 RNA, the RNA component of the human RNase P enzyme, appended to a nonimported RNA directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both noncoding RNAs, such as tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix. In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA of human mitochondrial ribosomal protein S12 (MRPS12), contain regulatory sequences in their 3′-untranslated region (UTR) that confers localization to the mitochondrial outer membrane, which is postulated to aid in protein translocation after translation. We show that for some mitochondrial-encoded transcripts, such as COX2, a 3′-UTR localization sequence is not required for mRNA import, whereas for corrective mitochondrial-encoded tRNAs, appending the 3′-UTR localization sequence was essential for efficient fusion-transcript translocation into mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines. Thus, this study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence that interacts with PNPASE, with or without a mitochondrial localization sequence, providing an exciting, general approach for overcoming mitochondrial genetic disorders.

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Section: Resultsmentioning

confidence: 95%

Correcting human mitochondrial mutations with targeted RNA import

Wang¹,

Shimada²,

Zhang³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

118

View full text Add to dashboard Cite

show abstract

“…3′ end processing is either accomplished by precise endonucleolytic cleavage too, or by the concerted action of multiple exo- and endonucleases [1], [2], [4]. The enzyme responsible for the first, exclusively endonucleolytic pathway is called RNase Z (or tRNase Z; EC 3.1.26.11) [2], [5]–[8].…”

Section: Introductionmentioning

confidence: 99%

Localization of Human RNase Z Isoforms: Dual Nuclear/Mitochondrial Targeting of the ELAC2 Gene Product by Alternative Translation Initiation

Rossmanith

2011

PLoS ONE

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RNase Z is an endonuclease responsible for the removal of 3′ extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase ZL) encoded by ELAC2, and a short form (RNase ZS; ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase ZS was found in the cytosol, whereas RNase ZL localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase ZL. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase ZL is the enzyme involved in both, nuclear and mitochondrial tRNA 3′ end maturation.

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“…They exist in two versions that are encoded by a conserved group of genes initially designated as ELAC1/ELAC2: a short form of RNase Z S (ELAC1) is found in all three domains of life, bacteria, archaea, and eukarya, while a long form of RNase Z L (ELAC2) is found only in the domain eukarya (Vogel et al, 2005;Ceballos and Vioque, 2007). The relative distribution of ELAC1/ELAC2 genes varies among eukaryotes.…”

Section: Introductionmentioning

confidence: 99%