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.
References
58
Referenced
609
10.1101/gr.1562804
10.1006/jmbi.1990.9999
10.1093/oxfordjournals.molbev.a026133
10.1126/science.1103388
10.1093/nar/gkj133
10.1038/nature01546
10.1016/0092-8674(92)90519-I
10.1016/0022-2836(90)90223-9
10.1006/jmbi.1997.0951
10.1126/science.1112014
10.1038/ng1789
10.1016/S0092-8674(04)00127-8
10.1126/science.1108625
10.1007/BF00278187
10.1101/gr.4222606
10.1126/science.1126316
10.1086/340787
10.1101/gr.1060303
10.1371/journal.pgen.0020037
10.1101/gr.3895005
10.1016/S1097-2765(00)80432-3
10.1101/gr.844103
10.1093/nar/gkj144
10.1016/j.tig.2005.03.007
10.1038/431757a
10.2307/1390807
10.1038/nature03001
10.1126/science.1068597
10.1126/science.1130164
10.1093/bioinformatics/18.8.1135
10.1371/journal.pcbi.0020005
10.1371/journal.pgen.0020062
10.1113/jphysiol.2006.113191
10.1038/sj.emboj.7601023
10.1016/S0378-1119(99)00324-8
10.1016/S0959-437X(99)80024-0
10.1101/gr.1011603
10.1038/nature01266
10.1006/geno.2001.6522
10.1093/nar/gni117
10.1016/j.tig.2005.10.003
10.1186/gb-2006-7-8-r78
10.1093/hmg/ddl182
/ Hum. Mol. Genet. / Signatures of adaptive evolution within human non-coding sequence by Ponting, (2006)10.1101/gr.4200206
10.1038/429510a
10.1101/gr.809403
10.1093/nar/gkl556
10.1101/gr.3715005
10.1038/415810a
10.1016/S0959-437X(99)00031-3
10.1073/pnas.0334222100
10.1073/pnas.87.12.4692
10.1038/nrm703
10.1093/nar/gkj115
10.1038/431757a
10.1038/nature01262
10.1126/science.1088305
10.1007/BF00178256
Dates
Type | When |
---|---|
Created | 18 years, 5 months ago (March 26, 2007, 9:04 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 18, 2021, 2:48 p.m.) |
Indexed | 14 hours, 58 minutes ago (Sept. 3, 2025, 6:20 a.m.) |
Issued | 18 years, 5 months ago (March 26, 2007) |
Published | 18 years, 5 months ago (March 26, 2007) |
Published Online | 18 years, 5 months ago (March 26, 2007) |
Published Print | 18 years, 4 months ago (May 1, 2007) |
@article{Ponjavic_2007, title={Functionality or transcriptional noise? Evidence for selection within long noncoding RNAs}, volume={17}, ISSN={1088-9051}, url={http://dx.doi.org/10.1101/gr.6036807}, DOI={10.1101/gr.6036807}, number={5}, journal={Genome Research}, publisher={Cold Spring Harbor Laboratory}, author={Ponjavic, Jasmina and Ponting, Chris P. and Lunter, Gerton}, year={2007}, month=mar, pages={556–565} }