Structural highlights
Function
SCAF4_HUMAN Anti-terminator protein required to prevent early mRNA termination during transcription (PubMed:31104839). Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins (PubMed:31104839). Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation (PubMed:31104839). Independently of SCAF8, also acts as a suppressor of transcriptional readthrough (PubMed:31104839).[1]
Publication Abstract from PubMed
The C-terminal domain (CTD) of RNA polymerase II serves as a binding platform for numerous enzymes and transcription factors involved in nascent RNA processing and the transcription cycle. The S2, S5-phosphorylated CTD is recognized by the transcription factor SCAF4, which functions as a transcription anti-terminator by preventing early mRNA transcript cleavage and polyadenylation. Here, we measured the binding affinities of differently modified CTD peptides by hSCAF4 and solved the complex structure of the hSCAF4-CTD-interaction domain (CID) bound to a S2, S5-quadra-phosphorylated CTD peptide. Our results revealed that the S2, S5-quadra-phosphorylated CTD peptide adopts a trans conformation and is located in a positively charged binding groove of hSCAF4-CID. Although hSCAF4-CID has almost the same binding pattern to the CTD as other CID-containing proteins, it preferentially binds to the S2, S5-phosphorylated CTD. Our findings provide insight into the regulatory mechanism of hSCAF4 in transcription termination.
Structural basis for the recognition of the S2, S5-phosphorylated RNA polymerase II CTD by the mRNA anti-terminator protein hSCAF4.,Zhou M, Ehsan F, Gan L, Dong A, Li Y, Liu K, Min J FEBS Lett. 2022 Jan;596(2):249-259. doi: 10.1002/1873-3468.14256. Epub 2021 Dec , 20. PMID:34897689[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gregersen LH, Mitter R, Ugalde AP, Nojima T, Proudfoot NJ, Agami R, Stewart A, Svejstrup JQ. SCAF4 and SCAF8, mRNA Anti-Terminator Proteins. Cell. 2019 Jun 13;177(7):1797-1813.e18. PMID:31104839 doi:10.1016/j.cell.2019.04.038
- ↑ Zhou M, Ehsan F, Gan L, Dong A, Li Y, Liu K, Min J. Structural basis for the recognition of the S2, S5-phosphorylated RNA polymerase II CTD by the mRNA anti-terminator protein hSCAF4. FEBS Lett. 2022 Jan;596(2):249-259. PMID:34897689 doi:10.1002/1873-3468.14256
