Loss of the mitochondrial protein-only ribonuclease P complex causes aberrant tRNA processing and lethality in Drosophila
Proteins encoded by mitochondrial DNA are translated using mitochondrially encoded tRNAs and rRNAs. As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is...
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Veröffentlicht in: | Nucleic acids research 2016-07, Vol.44 (13), p.6409-6422 |
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creator | Sen, Aditya Karasik, Agnes Shanmuganathan, Aranganathan Mirkovic, Elena Koutmos, Markos Cox, Rachel T |
description | Proteins encoded by mitochondrial DNA are translated using mitochondrially encoded tRNAs and rRNAs. As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP). However, its mechanism and impact on development is not yet known. Using homology searches, we have identified the three proteins composing Drosophila mt:RNase P: Mulder (PRORP), Scully (MRPP2) and Roswell (MRPP1). Here, we show that each protein is essential and localizes with mitochondria. Furthermore, reducing levels of each causes mitochondrial deficits, which appear to be due at least in part to defective mitochondrial tRNA processing. Overexpressing two members of the complex, Mulder and Roswell, is also lethal, and in the case of Mulder, causes abnormal mitochondrial morphology. These data are the first evidence that defective mt:RNase P causes mitochondrial dysfunction, lethality and aberrant mitochondrial tRNA processing in vivo, underscoring its physiological importance. This in vivo mt:RNase P model will advance our understanding of how loss of mitochondrial tRNA processing causes tissue failure, an important aspect of human mitochondrial disease. |
doi_str_mv | 10.1093/nar/gkw338 |
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As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP). However, its mechanism and impact on development is not yet known. Using homology searches, we have identified the three proteins composing Drosophila mt:RNase P: Mulder (PRORP), Scully (MRPP2) and Roswell (MRPP1). Here, we show that each protein is essential and localizes with mitochondria. Furthermore, reducing levels of each causes mitochondrial deficits, which appear to be due at least in part to defective mitochondrial tRNA processing. Overexpressing two members of the complex, Mulder and Roswell, is also lethal, and in the case of Mulder, causes abnormal mitochondrial morphology. These data are the first evidence that defective mt:RNase P causes mitochondrial dysfunction, lethality and aberrant mitochondrial tRNA processing in vivo, underscoring its physiological importance. This in vivo mt:RNase P model will advance our understanding of how loss of mitochondrial tRNA processing causes tissue failure, an important aspect of human mitochondrial disease.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkw338</identifier><identifier>PMID: 27131785</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>3-Hydroxyacyl CoA Dehydrogenases - genetics ; Animals ; DNA, Mitochondrial - genetics ; Drosophila - genetics ; Drosophila Proteins - genetics ; Gene Expression Regulation ; Humans ; Mitochondria - genetics ; Mitochondria - pathology ; Mitochondrial Proteins - genetics ; Ribonuclease P - genetics ; RNA ; RNA, Transfer - genetics ; Synthetic Lethal Mutations - genetics</subject><ispartof>Nucleic acids research, 2016-07, Vol.44 (13), p.6409-6422</ispartof><rights>Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.</rights><rights>Published by Oxford University Press on behalf of Nucleic Acids Research 2016. 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As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP). However, its mechanism and impact on development is not yet known. Using homology searches, we have identified the three proteins composing Drosophila mt:RNase P: Mulder (PRORP), Scully (MRPP2) and Roswell (MRPP1). Here, we show that each protein is essential and localizes with mitochondria. Furthermore, reducing levels of each causes mitochondrial deficits, which appear to be due at least in part to defective mitochondrial tRNA processing. Overexpressing two members of the complex, Mulder and Roswell, is also lethal, and in the case of Mulder, causes abnormal mitochondrial morphology. These data are the first evidence that defective mt:RNase P causes mitochondrial dysfunction, lethality and aberrant mitochondrial tRNA processing in vivo, underscoring its physiological importance. This in vivo mt:RNase P model will advance our understanding of how loss of mitochondrial tRNA processing causes tissue failure, an important aspect of human mitochondrial disease.</description><subject>3-Hydroxyacyl CoA Dehydrogenases - genetics</subject><subject>Animals</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Drosophila - genetics</subject><subject>Drosophila Proteins - genetics</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Mitochondria - genetics</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial Proteins - genetics</subject><subject>Ribonuclease P - genetics</subject><subject>RNA</subject><subject>RNA, Transfer - genetics</subject><subject>Synthetic Lethal Mutations - genetics</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1v1DAQhi0Eokvhwg9APiKkUDu2E-eCVLV8VFq1CMHZmngnG4NjB9uh7L8n1ZYKTnOYZ96Z0UPIS87ectaJswDpbP_jVgj9iGy4aOpKdk39mGyYYKriTOoT8izn74xxyZV8Sk7qlgvearUhh23MmcaBlhHp5Eq0Ywy75MDTOcWCLlQx-ANNro9hsR4hI_1MbZxmj7-phSVjptBjShAKLV-uz-8GLebswp5C2FGPZQTvyoG6QC9TzHEenYfn5MkAPuOL-3pKvn14__XiU7W9-Xh1cb6trOKyVLWQrIe62WmOugPNlJKD0tj2XEsUDHnXc9UIUTOEzkrWAFjdNLWEhnXDIE7Ju2PuvPQT7iyGksCbObkJ0sFEcOb_TnCj2cdfRtUdr5VYA17fB6T4c8FczOSyRe8hYFyy4Zq1umNt263omyNq1zdzwuFhDWfmzpVZXZmjqxV-9e9hD-hfOeIPbUaTiw</recordid><startdate>20160727</startdate><enddate>20160727</enddate><creator>Sen, Aditya</creator><creator>Karasik, Agnes</creator><creator>Shanmuganathan, Aranganathan</creator><creator>Mirkovic, Elena</creator><creator>Koutmos, Markos</creator><creator>Cox, Rachel T</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160727</creationdate><title>Loss of the mitochondrial protein-only ribonuclease P complex causes aberrant tRNA processing and lethality in Drosophila</title><author>Sen, Aditya ; Karasik, Agnes ; Shanmuganathan, Aranganathan ; Mirkovic, Elena ; Koutmos, Markos ; Cox, Rachel T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-2340ba26d81e89a80554f58e7b184e30e19b1563320ea9c406aac86624a609ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3-Hydroxyacyl CoA Dehydrogenases - genetics</topic><topic>Animals</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Drosophila - genetics</topic><topic>Drosophila Proteins - genetics</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Mitochondria - genetics</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Ribonuclease P - genetics</topic><topic>RNA</topic><topic>RNA, Transfer - genetics</topic><topic>Synthetic Lethal Mutations - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sen, Aditya</creatorcontrib><creatorcontrib>Karasik, Agnes</creatorcontrib><creatorcontrib>Shanmuganathan, Aranganathan</creatorcontrib><creatorcontrib>Mirkovic, Elena</creatorcontrib><creatorcontrib>Koutmos, Markos</creatorcontrib><creatorcontrib>Cox, Rachel T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sen, Aditya</au><au>Karasik, Agnes</au><au>Shanmuganathan, Aranganathan</au><au>Mirkovic, Elena</au><au>Koutmos, Markos</au><au>Cox, Rachel T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of the mitochondrial protein-only ribonuclease P complex causes aberrant tRNA processing and lethality in Drosophila</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2016-07-27</date><risdate>2016</risdate><volume>44</volume><issue>13</issue><spage>6409</spage><epage>6422</epage><pages>6409-6422</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Proteins encoded by mitochondrial DNA are translated using mitochondrially encoded tRNAs and rRNAs. As with nuclear encoded tRNAs, mitochondrial tRNAs must be processed to become fully functional. The mitochondrial form of ribonuclease P (mt:RNase P) is responsible for 5'-end maturation and is comprised of three proteins; mitochondrial RNase P protein (MRPP) 1 and 2 together with proteinaceous RNase P (PRORP). However, its mechanism and impact on development is not yet known. Using homology searches, we have identified the three proteins composing Drosophila mt:RNase P: Mulder (PRORP), Scully (MRPP2) and Roswell (MRPP1). Here, we show that each protein is essential and localizes with mitochondria. Furthermore, reducing levels of each causes mitochondrial deficits, which appear to be due at least in part to defective mitochondrial tRNA processing. Overexpressing two members of the complex, Mulder and Roswell, is also lethal, and in the case of Mulder, causes abnormal mitochondrial morphology. These data are the first evidence that defective mt:RNase P causes mitochondrial dysfunction, lethality and aberrant mitochondrial tRNA processing in vivo, underscoring its physiological importance. This in vivo mt:RNase P model will advance our understanding of how loss of mitochondrial tRNA processing causes tissue failure, an important aspect of human mitochondrial disease.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>27131785</pmid><doi>10.1093/nar/gkw338</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | 3-Hydroxyacyl CoA Dehydrogenases - genetics Animals DNA, Mitochondrial - genetics Drosophila - genetics Drosophila Proteins - genetics Gene Expression Regulation Humans Mitochondria - genetics Mitochondria - pathology Mitochondrial Proteins - genetics Ribonuclease P - genetics RNA RNA, Transfer - genetics Synthetic Lethal Mutations - genetics |
title | Loss of the mitochondrial protein-only ribonuclease P complex causes aberrant tRNA processing and lethality in Drosophila |
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