Direct measurement of pervasive weak repression by microRNAs and their role at the network level
Abstract Background A gene regulatory network (GRN) comprises many weak links that are often regulated by microRNAs. Since miRNAs rarely repress their target genes by more than 30%, doubts have been expressed about the biological relevance of such weak effects. These doubts raise the possibility of...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4757-z |
| _version_ | 1818034513124524032 |
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| author | Fuqiang Ma Pei Lin Qingjian Chen Xuemei Lu Yong E. Zhang Chung-I Wu |
| author_facet | Fuqiang Ma Pei Lin Qingjian Chen Xuemei Lu Yong E. Zhang Chung-I Wu |
| author_sort | Fuqiang Ma |
| collection | DOAJ |
| description | Abstract Background A gene regulatory network (GRN) comprises many weak links that are often regulated by microRNAs. Since miRNAs rarely repress their target genes by more than 30%, doubts have been expressed about the biological relevance of such weak effects. These doubts raise the possibility of under-estimation as miRNA repression is usually estimated indirectly from equilibrium expression levels. Results To measure miRNA repression directly, we inhibited transcript synthesis in Drosophila larvae and collected time-course data on mRNA abundance, the decline of which reflects transcript degradation. The rate of target degradation in the absence of miR310s, a moderately expressed miRNA family, was found to decrease by 5 to 15%. A conventional analysis that does not remove transcript synthesis yields an estimate of 6.5%, within the range of the new estimates. These data permit further examinations of the repression mechanisms by miRNAs including seed matching types, APA (alternative polyadenylation) sites, effects of other highly-expressed miRNAs and the length of 3’UTR. Our direct measurements suggest the latter two factors have a measurable effect on decay rate. Conclusion The direct measurement confirms pervasive weak repression by miRNAs, supporting the conclusions based on indirect assays. The confirmation suggests that this weak repression may indeed be miRNAs’ main function. In this context, we discuss the recent proposal that weak repression is “cumulatively powerful” in stabilizing GRNs. |
| first_indexed | 2024-12-10T06:40:21Z |
| format | Article |
| id | doaj.art-96454d5da11940a4a0f9d147c446e69c |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-10T06:40:21Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-96454d5da11940a4a0f9d147c446e69c2022-12-22T01:58:49ZengBMCBMC Genomics1471-21642018-05-0119111210.1186/s12864-018-4757-zDirect measurement of pervasive weak repression by microRNAs and their role at the network levelFuqiang Ma0Pei Lin1Qingjian Chen2Xuemei Lu3Yong E. Zhang4Chung-I Wu5Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of SciencesSchool of Life Science, Sun Yat-Sen UniversitySchool of Life Science, Sun Yat-Sen UniversityKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of SciencesUniversity of Chinese Academy of SciencesKey Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of SciencesAbstract Background A gene regulatory network (GRN) comprises many weak links that are often regulated by microRNAs. Since miRNAs rarely repress their target genes by more than 30%, doubts have been expressed about the biological relevance of such weak effects. These doubts raise the possibility of under-estimation as miRNA repression is usually estimated indirectly from equilibrium expression levels. Results To measure miRNA repression directly, we inhibited transcript synthesis in Drosophila larvae and collected time-course data on mRNA abundance, the decline of which reflects transcript degradation. The rate of target degradation in the absence of miR310s, a moderately expressed miRNA family, was found to decrease by 5 to 15%. A conventional analysis that does not remove transcript synthesis yields an estimate of 6.5%, within the range of the new estimates. These data permit further examinations of the repression mechanisms by miRNAs including seed matching types, APA (alternative polyadenylation) sites, effects of other highly-expressed miRNAs and the length of 3’UTR. Our direct measurements suggest the latter two factors have a measurable effect on decay rate. Conclusion The direct measurement confirms pervasive weak repression by miRNAs, supporting the conclusions based on indirect assays. The confirmation suggests that this weak repression may indeed be miRNAs’ main function. In this context, we discuss the recent proposal that weak repression is “cumulatively powerful” in stabilizing GRNs.http://link.springer.com/article/10.1186/s12864-018-4757-zmRNA degradationMiR310sTargetsWeak repressionNetwork |
| spellingShingle | Fuqiang Ma Pei Lin Qingjian Chen Xuemei Lu Yong E. Zhang Chung-I Wu Direct measurement of pervasive weak repression by microRNAs and their role at the network level BMC Genomics mRNA degradation MiR310s Targets Weak repression Network |
| title | Direct measurement of pervasive weak repression by microRNAs and their role at the network level |
| title_full | Direct measurement of pervasive weak repression by microRNAs and their role at the network level |
| title_fullStr | Direct measurement of pervasive weak repression by microRNAs and their role at the network level |
| title_full_unstemmed | Direct measurement of pervasive weak repression by microRNAs and their role at the network level |
| title_short | Direct measurement of pervasive weak repression by microRNAs and their role at the network level |
| title_sort | direct measurement of pervasive weak repression by micrornas and their role at the network level |
| topic | mRNA degradation MiR310s Targets Weak repression Network |
| url | http://link.springer.com/article/10.1186/s12864-018-4757-z |
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