CoChat
Sign Up
PreprintCited by 2RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

RBBP6 activates the pre-mRNA 3’-end processing machinery in humans

Open access
Boreikaite, Vytaute, Elliott, Thomas, Chin, Jason, Passmore, Lori A·2021·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2021.11.02.466915

Preprint — published as 10.1101/gad.349223.121

Open this paper in CoChat — free accountOpen PDF

Abstract

3’-end processing of most human mRNAs is carried out by the cleavage and polyadenylation specificity factor (CPSF; CPF in yeast). Endonucleolytic cleavage of the nascent pre-mRNA defines the 3’-end of the mature transcript, which is important for mRNA localization, translation and stability. Cleavage must therefore be tightly regulated. Here, we reconstitute specific and efficient 3’-endonuclease activity of human CPSF with purified proteins. This requires the sevensubunit CPSF as well as three additional protein factors: cleavage stimulatory factor (CStF), cleavage factor IIm (CFIIm) and, importantly, the multi-domain protein RBBP6. Unlike its yeast homologue Mpe1, which is a stable subunit of CPF, RBBP6 does not copurify with CPSF and is recruited in an RNA-dependent manner. Sequence and mutational analyses suggest that RBBP6 interacts with the WDR33 and CPSF73 subunits of CPSF. Thus, it is likely that the role of RBBP6 is conserved from yeast to human. Overall, our data are consistent with CPSF endonuclease activation and site-specific pre-mRNA cleavage being highly controlled to maintain fidelity in RNA processing.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/2021.11.02.466915

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 59

  1. 10.1074/jbc.M505532200 · DOI
  2. 10.1016/j.molcel.2014.08.005 · DOI
  3. 2018, Protein interaction mapping identifies RBBP6 as a negative regulator of Ebola virus replication, Cell, 175, 1917, 10.1016/j.cell.2018.08.044 · DOI
  4. 10.1101/gr.10.7.1001 · DOI
  5. 10.1016/j.ceb.2005.04.003 · DOI
  6. 10.1126/science.aao6535 · DOI
  7. 10.1101/gad.250993.114 · DOI
  8. 10.7554/eLife.20010 · DOI
  9. 10.1038/s41594-017-0020-6 · DOI
  10. 10.4161/nucl.36360 · DOI
  11. 10.1073/pnas.0601091103 · DOI
  12. 10.1101/gad.308528.117 · DOI
  13. 10.1101/gad.245787.114 · DOI
  14. 10.1021/bi200964p · DOI · Paper page
  15. 10.1016/S1097-2765(00)80076-3 · DOI
  16. 2019, Alternative cleavage and polyadenylation in health and disease, Nat. Rev. Genet, 20, 599, 10.1038/s41576-019-0145-z · DOI
  17. 10.1261/rna.078764.121 · DOI
  18. 10.1261/rna.070870.119 · DOI
  19. 10.1016/j.molcel.2018.12.023 · DOI
  20. Hocine, S. , Singer, R.H. , and Grünwald, D. (2010). RNA processing and export. Cold Spring Harb. Perspect. Biol. 2. · DOI
  21. 10.1097/QCO.0b013e32834c630e · DOI
  22. 10.1016/j.bbrc.2019.08.004 · DOI
  23. 10.1038/sj.emboj.7600070 · DOI
  24. 10.1038/embor.2008.146 · DOI
  25. 10.1016/j.sbi.2019.08.001 · DOI
  26. 10.1101/gad.348671.121 · DOI
  27. Kwon, B. , Patel, N.D. , Lee, S.H. , Lee, J. , Ma, W. , and Mayr, C. (2021). Enhancers regulate polyadenylation site cleavage and control 3’UTR isoform expression. bioRxiv, 2020.08.17.254193.
  28. 10.1128/MCB.00077-14 · DOI
  29. 10.1073/pnas.0701916104 · DOI
  30. 2021, On the cutting edge: regulation and therapeutic potential of the mRNA 3’ end nuclease, Trends Biochem. Sci, 46, 772, 10.1016/j.tibs.2021.04.003 · DOI
  31. 10.1038/nature05363 · DOI
  32. 10.1016/j.celrep.2012.05.003 · DOI
  33. 10.1016/S0092-8674(85)80065-9 · DOI
  34. 10.15252/emmm.201607370 · DOI
  35. 10.1038/s41580-021-00417-y · DOI
  36. Rodríguez-Molina, J.B. , O’Reilly, F.J. , Sheekey, E. , Maslen, S. , Skehel, J.M. , Rappsilber, J. , and Passmore, L.A. (2021). Mpe1 senses the polyadenylation signal in pre-mRNA to control cleavage and polyadenylation. bioRxiv, 2021.09.02.458805. · DOI
  37. 10.1038/s41589-019-0424-1 · DOI
  38. 1987, Requirements for accurate and efficient mRNA 3’ end cleavage and polyadenylation of a simian virus 40 early pre-RNA in vitro, Mol. Cell. Biol, 7, 495
  39. 10.1006/geno.1995.1084 · DOI
  40. 10.1006/geno.1995.0017 · DOI
  41. 10.1261/rna.068056.118 · DOI
  42. 10.1101/gad.250985.114 · DOI
  43. 10.1128/MCB.7.4.1518 · DOI
  44. 10.1016/j.molcel.2008.12.028 · DOI
  45. 10.1038/sj.onc.1200825 · DOI
  46. 10.1038/ncomms14574 · DOI
  47. 2018, Molecular basis for the recognition of the human AAUAAA polyadenylation signal, Proc. Natl. Acad. Sci. U. S. A, 115, 1419, 10.1073/pnas.1718723115 · DOI
  48. 10.1126/science.aaz7758 · DOI
  49. 10.1126/scitranslmed.aax7161 · DOI
  50. 10.1101/gad.4.12a.2112 · DOI
  51. 10.1128/MCB.17.7.3907 · DOI
  52. 10.1016/S1097-2765(00)80291-9 · DOI
  53. 2012, Signals for pre-mRNA cleavage and polyadenylation, Wiley Interdiscip. Rev. RNA, 3, 385, 10.1002/wrna.116 · DOI
  54. Tseng, H.-W. , Mota-Sydor, A. , Leventis, R. , Topisirovic, I. , and Duchaine, T.F. (2021). Distinct, opposing functions for CFIm59 and CFIm68 in mRNA alternative polyadenylation of Pten and in the PI3K/Akt signalling cascade. bioRxiv, 2021.09.09.459613. · DOI
  55. 10.1128/MCB.21.24.8346-8356.2001 · DOI
  56. 10.1093/emboj/19.21.5895 · DOI
  57. 2016, biGBac enables rapid gene assembly for the expression of large multisubunit protein complexes, Proc. Natl. Acad. Sci, 113, 2564, 10.1073/pnas.1604935113 · DOI
  58. 2020, Structural insights into the human pre-mRNA 3’-end processing machinery, Mol. Cell, 77, 1
  59. 10.1016/j.molcel.2017.11.031 · DOI

Metadata

Authors
Boreikaite, V., Elliott, T., Chin, J., & Passmore, L. A.
Affiliations
MRC Laboratory of Molecular Biology (GB)
Corresponding author
Passmore, Lori A
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2021-11-02
DOI
10.1101/2021.11.02.466915
OpenAlex
W3208027327
Cited by
2
References
1
Citations by year
2024: 1 · 2023: 1
Type
posted content
Language
en
Open access
Licence
cc-by-nc
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • University of Cambridge
  • European Commission (HORIZON2020)
  • Medical Research Council (MC_U105181009, 725685, MC_U105192715, MC_UP_A024_1008)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords
RBBP6, pre-mRNA 3' end processing, cleavage and polyadenylation specificity factor, CPSF73, polyadenylation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review