Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs
Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent “transcriptional noise.” Here, we describe an analysis...
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| Published in | Genome Research Vol. 17; no. 5; pp. 556 - 565 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Cold Spring Harbor Laboratory Press
01.05.2007
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1088-9051 1549-5469 1549-5477 |
| DOI | 10.1101/gr.6036807 |
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| Abstract | Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent “transcriptional noise.” Here, we describe an analysis of 3122 long and full-length, noncoding RNAs (“macroRNAs”) from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs’ promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%–5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs’ functions. |
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| AbstractList | Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent "transcriptional noise." Here, we describe an analysis of 3122 long and full-length, noncoding RNAs ("macroRNAs") from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs' promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%-5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs' functions. Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent "transcriptional noise." Here, we describe an analysis of 3122 long and full-length, noncoding RNAs ("macroRNAs") from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs' promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%-5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs' functions.Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of evidence of their functionality, thereby leaving an impression that, instead, they represent "transcriptional noise." Here, we describe an analysis of 3122 long and full-length, noncoding RNAs ("macroRNAs") from the mouse, and compare their sequences and their promoters with orthologous sequence from human and from rat. We considered three independent signatures of purifying selection related to substitutions, sequence insertions and deletions, and splicing. We find that the evolution of the set of noncoding RNAs is not consistent with neutralist explanations. Rather, our results indicate that purifying selection has acted on the macroRNAs' promoters, primary sequence, and consensus splice site motifs. Promoters have experienced the greatest elimination of nucleotide substitutions, insertions, and deletions. The proportion of conserved sequence (4.1%-5.5%) in these macroRNAs is comparable to the density of exons within protein-coding transcripts (5.2%). These macroRNAs, taken together, thus possess the imprint of purifying selection, thereby indicating their functionality. Our findings should now provide an incentive for the experimental investigation of these macroRNAs' functions. |
| Author | Ponjavic, Jasmina Lunter, Gerton Ponting, Chris P. |
| AuthorAffiliation | MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom |
| AuthorAffiliation_xml | – name: MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom |
| Author_xml | – sequence: 1 givenname: Jasmina surname: Ponjavic fullname: Ponjavic, Jasmina – sequence: 2 givenname: Chris P. surname: Ponting fullname: Ponting, Chris P. – sequence: 3 givenname: Gerton surname: Lunter fullname: Lunter, Gerton |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17387145$$D View this record in MEDLINE/PubMed |
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| Snippet | Long transcripts that do not encode protein have only rarely been the subject of experimental scrutiny. Presumably, this is owing to the current lack of... |
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| SubjectTerms | Animals Consensus Sequence Conserved Sequence Databases, Genetic DNA, Intergenic - genetics Humans Mice Point Mutation Promoter Regions, Genetic Rats RNA Splice Sites RNA, Untranslated - genetics Selection, Genetic Transcription, Genetic |
| Title | Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/17387145 https://www.proquest.com/docview/19663947 https://www.proquest.com/docview/70474160 https://pubmed.ncbi.nlm.nih.gov/PMC1855172 |
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