8R8R
Cryo-EM structure of the human mPSF with PAPOA C-terminus peptide (PAPOAc)
Summary for 8R8R
| Entry DOI | 10.2210/pdb8r8r/pdb |
| EMDB information | 19008 |
| Descriptor | Cleavage and polyadenylation specificity factor subunit 1, pre-mRNA 3' end processing protein WDR33, Cleavage and polyadenylation specificity factor subunit 4, ... (6 entities in total) |
| Functional Keywords | 3-end processing, polyadenylation, papoa, pre-mrna, cleavage and polyadenylation, rna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 245363.66 |
| Authors | Todesca, S.,Sandmeir, F.,Keidel, A.,Conti, E. (deposition date: 2023-11-29, release date: 2024-04-10, Last modification date: 2024-06-26) |
| Primary citation | Todesca, S.,Sandmeir, F.,Keidel, A.,Conti, E. Molecular basis of human poly(A) polymerase recruitment by mPSF. Rna, 30:795-806, 2024 Cited by PubMed Abstract: 3' end processing of most eukaryotic precursor-mRNAs (pre-mRNAs) is a crucial cotranscriptional process that generally involves the cleavage and polyadenylation of the precursor transcripts. Within the human 3' end processing machinery, the four-subunit mammalian polyadenylation specificity factor (mPSF) recognizes the polyadenylation signal (PAS) in the pre-mRNA and recruits the poly(A) polymerase α (PAPOA) to it. To shed light on the molecular mechanisms of PAPOA recruitment to mPSF, we used a combination of cryogenic-electron microscopy (cryo-EM) single-particle analysis, computational structure prediction, and in vitro biochemistry to reveal an intricate interaction network. A short linear motif in the mPSF subunit FIP1 interacts with the structured core of human PAPOA, with a binding mode that is evolutionarily conserved from yeast to human. In higher eukaryotes, however, PAPOA contains a conserved C-terminal motif that can interact intramolecularly with the same residues of the PAPOA structured core used to bind FIP1. Interestingly, using biochemical assay and cryo-EM structural analysis, we found that the PAPOA C-terminal motif can also directly interact with mPSF at the subunit CPSF160. These results show that PAPOA recruitment to mPSF is mediated by two distinct intermolecular connections and further suggest the presence of mutually exclusive interactions in the regulation of 3' end processing. PubMed: 38538052DOI: 10.1261/rna.079915.123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.79 Å) |
Structure validation
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