Regulatory controls of microRNA genes beyond the mature microRNAs
Abstract/Contents
- Abstract
- MicroRNA (miRNA) genes, which encode an abundant class of ~22-nucleotide (nt), evolutionarily conserved small RNAs, control a fundamental layer of genetic programs at the post-transcriptional level. However, little is known about how the activity of miRNA genes is regulated and how the regulatory information controlling their activity is encoded. Interestingly, mature miRNAs can often be classified into large families consisting of members with identical seeds (nucleotides 2 through 8 of the mature miRNAs) and highly homologous ~22-nt mature miRNA sequences, but with divergent sequences and structural elements beyond their mature miRNAs. Here we investigated whether members of a miRNA gene family that encode identical or nearly identical mature miRNAs are functionally interchangeable in vivo and if not, why? We compare the activities of the mir-181 gene family in promoting double positive T cell development and show that miRNA genes that encode identical to nearly identical mature miRNAs can have distinct activities. The differences in activity between mir-181a-1 and mir-181c are largely determined by their unique primary/precursor-miRNA (pri/pre-miRNA) loop nucleotides, and the differences in activity between mir-181a-1 and mir-181b-1 are determined by both the pri/pre-miRNA loop and stem. Furthermore, the organization of mir-181a-1/b-1 in a cluster is important for its full activity. We also show that mir-181 family members can differentially regulate target genes quantitatively, and that some target genes can be upregulated. Taken together, we have demonstrated that regulatory information encoded in a miRNA gene beyond the mature miRNA plays a critical role in controlling the activity of the miRNA gene, suggesting that miRNA family members could have evolved different functions through their divergent miRNA gene sequences and structural elements beyond their mature miRNAs. Although, proteins may have evolved to recognize the structural and sequence elements of the pri/pre-miRNAs, we suggest that the regulatory information encoded in the structured pri/pre-miRNA may be directly interpreted through target and pri/pre-miRNA interactions.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Liu, Gwen |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology. |
| Primary advisor | Chen, Chang-Zheng |
| Thesis advisor | Chen, Chang-Zheng |
| Thesis advisor | Blau, Helen M |
| Thesis advisor | Fire, Andrew Zachary |
| Thesis advisor | Sarnow, P. (Peter) |
| Advisor | Blau, Helen M |
| Advisor | Fire, Andrew Zachary |
| Advisor | Sarnow, P. (Peter) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Gwen Liu. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Ph. D. Stanford University 2010 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Gwen Liu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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