The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells
Open accessAbstract
3′ end formation of pre-mRNAs is coupled to their transcription via the C-terminal domain (CTD) of RNA polymerase II (Pol II). Nearly all protein-coding transcripts are matured by cleavage and polyadenylation (CPA), which is frequently misregulated in disease. Understanding how transcription is coordinated with CPA in human cells is therefore very important. We found that the CTD is heavily phosphorylated on Ser2 (Ser2p) at poly(A) (pA) signals coincident with recruitment of the CstF77 CPA factor. Depletion of the Ser2 kinase Cdk12 impairs Ser2p, CstF77 recruitment, and CPA, strongly suggesting that the processes are linked, as they are in budding yeast. Importantly, we additionally show that the high Ser2p signals at the 3′ end depend on pA signal function. Down-regulation of CPA results in the loss of a 3′ Ser2p peak, whereas a new peak is formed when CPA is induced de novo. Finally, high Ser2p signals are generated by Pol II pausing, which is a well-known feature of pA site recognition. Thus, a reciprocal relationship between early steps in pA site processing and Ser2p ensures efficient 3′ end formation.
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Cites
RNA-Guided Human Genome Engineering via Cas9
Mali, P., Yang, L., Esvelt, K. M., Aach, J., Guell, M., DiCarlo, J. E., Norville, J. E., & Church, G. M. (2013) · Science · doi:10.1126/science.1232033 · Cited by 9,210
Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression
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CRISPR-Mediated Modular RNA-Guided Regulation of Transcription in Eukaryotes
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“If a catalytically dead Cas9 (dCas9) is expressed, the complex remains bound to the DNA, where it impedes Pol II progress (Gilbert et al. 2013; Qi et al. 2013).”
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U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
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Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors
Zhang, T., Kwiatkowski, N., Olson, C. M., Dixon-Clarke, S. E., Abraham, B. J., Greifenberg, A. K., Ficarro, S. B., Elkins, J. M., Liang, Y., Hannett, N. M., et al. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2166 · Cited by 374
CDK12 regulates DNA repair genes by suppressing intronic polyadenylation
Dubbury, S. J., Boutz, P. L., & Sharp, P. A. (2018) · Nature · doi:10.1038/s41586-018-0758-y · Cited by 318
Cortazar, M. A., Sheridan, R. M., Erickson, B., Fong, N., Glover-Cutter, K., Brannan, K., & Bentley, D. L. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.031 · Cited by 227
Structural and functional analysis of the Cdk13/Cyclin K complex
Greifenberg, A. K., Hönig, D., Pilarova, K., Düster, R., Bartholomeeusen, K., Bösken, C. A., Anand, K., Blazek, D., & Geyer, M. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.025 · Cited by 157
Metadata
- Authors
- Davidson, L., Muniz, L., & West, S.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-01-29
- Volume
- 28
- Issue
- 4
- Pages
- 342-356
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2118585964
- Cited by
- 170
- References
- 7
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: 3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. https://app.cochat.ai/papers/10.1101/gad.231274.113
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- Davidson, L., Muniz, L., & West, S. (2014). 3′ end formation of pre-mRNA and phosphorylation of Ser2 on the RNA polymerase II CTD are reciprocally coupled in human cells. Genes & Development. https://doi.org/10.1101/gad.231274.113
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