Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination
New evidence indicates that termination of transcription is an important regulatory step, closely related to transcriptional interference 1 and even transcriptional initiation 2 . However, how this occurs is poorly understood. Recently, in vivo analysis of transcriptional termination for the human β...
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| Veröffentlicht in: | Nature (London) 2004-11, Vol.432 (7016), p.526-530 |
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| creator | Teixeira, Alexandre Tahiri-Alaoui, Abdessamad West, Steve Thomas, Benjamin Ramadass, Aroul Martianov, Igor Dye, Mick James, William Proudfoot, Nick J. Akoulitchev, Alexandre |
| description | New evidence indicates that termination of transcription is an important regulatory step, closely related to transcriptional interference
1
and even transcriptional initiation
2
. However, how this occurs is poorly understood. Recently,
in vivo
analysis of transcriptional termination for the human β-globin gene revealed a new phenomenon—co-transcriptional cleavage (CoTC)
3
. This primary cleavage event within β-globin pre-messenger RNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II
3
. Here we show that the CoTC process in the human β-globin gene involves an RNA self-cleaving activity. We characterize the autocatalytic core of the CoTC ribozyme and show its functional role in efficient termination
in vivo
. The identified core CoTC is highly conserved in the 3′ flanking regions of other primate β-globin genes. Functionally, it resembles the 3′ processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes
Didymium iridis
and
Physarum polycephalum
, indicating evolutionary conservation of this molecular process. We predict that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide the entry point for exonucleases involved in mRNA maturation, turnover and, in particular, transcriptional termination. |
| doi_str_mv | 10.1038/nature03032 |
| format | Article |
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1
and even transcriptional initiation
2
. However, how this occurs is poorly understood. Recently,
in vivo
analysis of transcriptional termination for the human β-globin gene revealed a new phenomenon—co-transcriptional cleavage (CoTC)
3
. This primary cleavage event within β-globin pre-messenger RNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II
3
. Here we show that the CoTC process in the human β-globin gene involves an RNA self-cleaving activity. We characterize the autocatalytic core of the CoTC ribozyme and show its functional role in efficient termination
in vivo
. The identified core CoTC is highly conserved in the 3′ flanking regions of other primate β-globin genes. Functionally, it resembles the 3′ processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes
Didymium iridis
and
Physarum polycephalum
, indicating evolutionary conservation of this molecular process. We predict that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide the entry point for exonucleases involved in mRNA maturation, turnover and, in particular, transcriptional termination.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature03032</identifier><identifier>PMID: 15565159</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Algorithms ; Base Sequence ; Biological and medical sciences ; Catalysis ; Cellular biology ; Computational Biology ; Fundamental and applied biological sciences. Psychology ; Genes ; Globins - genetics ; HeLa Cells ; Humanities and Social Sciences ; Humans ; letter ; Molecular and cellular biology ; Molecular genetics ; Molecular Sequence Data ; multidisciplinary ; Ribonucleic acid ; RNA ; RNA Precursors - genetics ; RNA Precursors - metabolism ; RNA, Catalytic - genetics ; RNA, Catalytic - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Science ; Science (multidisciplinary) ; Transcription, Genetic - genetics ; Transcription. Transcription factor. Splicing. Rna processing</subject><ispartof>Nature (London), 2004-11, Vol.432 (7016), p.526-530</ispartof><rights>Macmillan Magazines Ltd. 2004</rights><rights>2005 INIST-CNRS</rights><rights>COPYRIGHT 2004 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Nov 25, 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-9d28d75a0fcc26d1b31c339b9f7340b8ae1a02f5e16a4e540f337f94d71331d33</citedby><cites>FETCH-LOGICAL-c653t-9d28d75a0fcc26d1b31c339b9f7340b8ae1a02f5e16a4e540f337f94d71331d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature03032$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature03032$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16305240$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15565159$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teixeira, Alexandre</creatorcontrib><creatorcontrib>Tahiri-Alaoui, Abdessamad</creatorcontrib><creatorcontrib>West, Steve</creatorcontrib><creatorcontrib>Thomas, Benjamin</creatorcontrib><creatorcontrib>Ramadass, Aroul</creatorcontrib><creatorcontrib>Martianov, Igor</creatorcontrib><creatorcontrib>Dye, Mick</creatorcontrib><creatorcontrib>James, William</creatorcontrib><creatorcontrib>Proudfoot, Nick J.</creatorcontrib><creatorcontrib>Akoulitchev, Alexandre</creatorcontrib><title>Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>New evidence indicates that termination of transcription is an important regulatory step, closely related to transcriptional interference
1
and even transcriptional initiation
2
. However, how this occurs is poorly understood. Recently,
in vivo
analysis of transcriptional termination for the human β-globin gene revealed a new phenomenon—co-transcriptional cleavage (CoTC)
3
. This primary cleavage event within β-globin pre-messenger RNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II
3
. Here we show that the CoTC process in the human β-globin gene involves an RNA self-cleaving activity. We characterize the autocatalytic core of the CoTC ribozyme and show its functional role in efficient termination
in vivo
. The identified core CoTC is highly conserved in the 3′ flanking regions of other primate β-globin genes. Functionally, it resembles the 3′ processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes
Didymium iridis
and
Physarum polycephalum
, indicating evolutionary conservation of this molecular process. We predict that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide the entry point for exonucleases involved in mRNA maturation, turnover and, in particular, transcriptional termination.</description><subject>Algorithms</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Catalysis</subject><subject>Cellular biology</subject><subject>Computational Biology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genes</subject><subject>Globins - genetics</subject><subject>HeLa Cells</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>letter</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>multidisciplinary</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Precursors - genetics</subject><subject>RNA Precursors - metabolism</subject><subject>RNA, Catalytic - genetics</subject><subject>RNA, Catalytic - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Transcription, Genetic - genetics</subject><subject>Transcription. Transcription factor. Splicing. 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Psychology</topic><topic>Genes</topic><topic>Globins - genetics</topic><topic>HeLa Cells</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>letter</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>multidisciplinary</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Precursors - genetics</topic><topic>RNA Precursors - metabolism</topic><topic>RNA, Catalytic - genetics</topic><topic>RNA, Catalytic - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Transcription, Genetic - genetics</topic><topic>Transcription. Transcription factor. Splicing. 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1
and even transcriptional initiation
2
. However, how this occurs is poorly understood. Recently,
in vivo
analysis of transcriptional termination for the human β-globin gene revealed a new phenomenon—co-transcriptional cleavage (CoTC)
3
. This primary cleavage event within β-globin pre-messenger RNA, downstream of the poly(A) site, is critical for efficient transcriptional termination by RNA polymerase II
3
. Here we show that the CoTC process in the human β-globin gene involves an RNA self-cleaving activity. We characterize the autocatalytic core of the CoTC ribozyme and show its functional role in efficient termination
in vivo
. The identified core CoTC is highly conserved in the 3′ flanking regions of other primate β-globin genes. Functionally, it resembles the 3′ processive, self-cleaving ribozymes described for the protein-encoding genes from the myxomycetes
Didymium iridis
and
Physarum polycephalum
, indicating evolutionary conservation of this molecular process. We predict that regulated autocatalytic cleavage elements within pre-mRNAs may be a general phenomenon and that functionally it may provide the entry point for exonucleases involved in mRNA maturation, turnover and, in particular, transcriptional termination.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>15565159</pmid><doi>10.1038/nature03032</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2004-11, Vol.432 (7016), p.526-530 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743494258 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | Algorithms Base Sequence Biological and medical sciences Catalysis Cellular biology Computational Biology Fundamental and applied biological sciences. Psychology Genes Globins - genetics HeLa Cells Humanities and Social Sciences Humans letter Molecular and cellular biology Molecular genetics Molecular Sequence Data multidisciplinary Ribonucleic acid RNA RNA Precursors - genetics RNA Precursors - metabolism RNA, Catalytic - genetics RNA, Catalytic - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Science Science (multidisciplinary) Transcription, Genetic - genetics Transcription. Transcription factor. Splicing. Rna processing |
| title | Autocatalytic RNA cleavage in the human β-globin pre-mRNA promotes transcription termination |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T12%3A01%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Autocatalytic%20RNA%20cleavage%20in%20the%20human%20%CE%B2-globin%20pre-mRNA%20promotes%20transcription%20termination&rft.jtitle=Nature%20(London)&rft.au=Teixeira,%20Alexandre&rft.date=2004-11-25&rft.volume=432&rft.issue=7016&rft.spage=526&rft.epage=530&rft.pages=526-530&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature03032&rft_dat=%3Cgale_proqu%3EA186286551%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204570922&rft_id=info:pmid/15565159&rft_galeid=A186286551&rfr_iscdi=true |