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Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases
Open accessAbstract
The lifespan of a mammalian mRNA is determined, in part, by the binding of regulatory proteins and small RNA-guided complexes. The conserved endonuclease activity of Argonaute2 requires extensive complementarity between a small RNA and its target and is not used by animal microRNAs, which pair with their targets imperfectly. Here, we investigate the endonucleolytic function of Ago2 and other nucleases by transcriptome-wide profiling of mRNA cleavage products retaining 5′-phosphate groups in mouse ES. We detect a prominent signature of Ago2-dependent cleavage events and validate several such targets. Unexpectedly, a broader class of Ago2-independent cleavage sites is also observed, indicating participation of additional nucleases in site-specific mRNA cleavage. Within this class, we identify a cohort of Drosha-dependent mRNA cleavage events that functionally regulate mRNA levels in mES cells, including one in the Dgcr8 mRNA. Together, these results highlight the underappreciated role of endonucleolytic cleavage in controlling mRNA fates in mammals.
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Citations
Cites
A dicer-independent miRNA biogenesis pathway that requires Ago catalysis
Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., & Hannon, G. J. (2010) · Nature · doi:10.1038/nature09092 · Cited by 1,149
Self-citation
Cited by
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318
Regulation of microRNA biogenesis
Ha, M., & Kim, V. N. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3838 · Cited by 5,462
Regulation of microRNA function in animals
Gebert, L. F. R., & MacRae, I. J. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0045-7 · Cited by 2,284
Diversifying microRNA sequence and function
Ameres, S. L., & Zamore, P. D. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3611 · Cited by 1,175
Hsu, S.-D., Tseng, Y.-T., Shrestha, S., Lin, Y.-L., Khaleel, A., Chou, C.-H., Chu, C.-F., Huang, H.-Y., Lin, C.-M., Ho, S.-Y., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1266 · Cited by 1,041
Metadata
- Authors
- Karginov, F. V., Cheloufi, S., Chong, M. M. W., Stark, A., Smith, A. D., & Hannon, G. J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 38
- Issue
- 6
- Pages
- 781-788
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2152267176
- Cited by
- 186
- References
- 1
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Karginov, F. V., Cheloufi, S., Chong, M. M. W., Stark, A., Smith, A. D., & Hannon, G. J. (2010). Diverse Endonucleolytic Cleavage Sites in the Mammalian Transcriptome Depend upon MicroRNAs, Drosha, and Additional Nucleases. Molecular Cell. https://doi.org/10.1016/j.molcel.2010.06.001
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