Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing
Most metazoan microRNA (miRNA) target sites have perfect pairing to the seed region, located near the miRNA 5′ end. Although pairing to the 3′ region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that imp...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2012
|
| Online Access: | http://hdl.handle.net/1721.1/72450 https://orcid.org/0000-0002-3872-2856 |
| _version_ | 1826193368258969600 |
|---|---|
| author | Shin, Chanseok Nam, Jin-Wu Farh, Kyle Kai-How Chiang, H. Rosaria Shkumatava, Alena Bartel, David |
| author2 | move to dc.description.sponsorship |
| author_facet | move to dc.description.sponsorship Shin, Chanseok Nam, Jin-Wu Farh, Kyle Kai-How Chiang, H. Rosaria Shkumatava, Alena Bartel, David |
| author_sort | Shin, Chanseok |
| collection | MIT |
| description | Most metazoan microRNA (miRNA) target sites have perfect pairing to the seed region, located near the miRNA 5′ end. Although pairing to the 3′ region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that impart Argonaute-catalyzed mRNA cleavage. Here, we present “centered sites,” a class of miRNA target sites that lack both perfect seed pairing and 3′-compensatory pairing and instead have 11–12 contiguous Watson-Crick pairs to the center of the miRNA. Although centered sites can impart mRNA cleavage in vitro (in elevated Mg[superscript 2+]), in cells they repress protein output without consequential Argonaute-catalyzed cleavage. Our study also identified extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many miRNAs are evolutionarily conserved. |
| first_indexed | 2024-09-23T09:37:57Z |
| format | Article |
| id | mit-1721.1/72450 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:37:57Z |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/724502022-09-30T15:49:09Z Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing Shin, Chanseok Nam, Jin-Wu Farh, Kyle Kai-How Chiang, H. Rosaria Shkumatava, Alena Bartel, David move to dc.description.sponsorship Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Bartel, David Shin, Chanseok Nam, Jin-Wu Farh, Kyle Kai-How Chiang, H. Rosaria Shkumatava, Alena Bartel, David Most metazoan microRNA (miRNA) target sites have perfect pairing to the seed region, located near the miRNA 5′ end. Although pairing to the 3′ region sometimes supplements seed matches or compensates for mismatches, pairing to the central region has been known to function only at rare sites that impart Argonaute-catalyzed mRNA cleavage. Here, we present “centered sites,” a class of miRNA target sites that lack both perfect seed pairing and 3′-compensatory pairing and instead have 11–12 contiguous Watson-Crick pairs to the center of the miRNA. Although centered sites can impart mRNA cleavage in vitro (in elevated Mg[superscript 2+]), in cells they repress protein output without consequential Argonaute-catalyzed cleavage. Our study also identified extensively paired sites that are cleavage substrates in cultured cells and human brain. This expanded repertoire of cleavage targets and the identification of the centered site type help explain why central regions of many miRNAs are evolutionarily conserved. National Institutes of Health (U.S.) Damon Runyon Cancer Research Foundation. Fellowship Award 2012-08-30T14:28:00Z 2012-08-30T14:28:00Z 2010-06 2010-04 Article http://purl.org/eprint/type/JournalArticle 1097-2765 http://hdl.handle.net/1721.1/72450 Shin, Chanseok et al. “Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing.” Molecular Cell 38.6 (2010): 789–802. https://orcid.org/0000-0002-3872-2856 en_US http://dx.doi.org/10.1016/j.molcel.2010.06.005 Molecular Cell Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier PMC |
| spellingShingle | Shin, Chanseok Nam, Jin-Wu Farh, Kyle Kai-How Chiang, H. Rosaria Shkumatava, Alena Bartel, David Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title | Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title_full | Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title_fullStr | Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title_full_unstemmed | Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title_short | Expanding the MicroRNA Targeting Code: Functional Sites with Centered Pairing |
| title_sort | expanding the microrna targeting code functional sites with centered pairing |
| url | http://hdl.handle.net/1721.1/72450 https://orcid.org/0000-0002-3872-2856 |
| work_keys_str_mv | AT shinchanseok expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing AT namjinwu expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing AT farhkylekaihow expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing AT chianghrosaria expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing AT shkumatavaalena expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing AT barteldavid expandingthemicrornatargetingcodefunctionalsiteswithcenteredpairing |