| Structural highlights
Function
TET5C_HUMAN Nucleotidyltransferase that act as a non-canonical poly(A) RNA polymerase which enhances mRNA stability and gene expression. Mainly targets mRNAs encoding endoplasmic reticulum-targeted protein and may be involved in induction of cell death.[1] [2] (Microbial infection) Seems to enhance replication of some viruses, including yellow fever virus, in response to type I interferon.[3]
Publication Abstract from PubMed
The FAM46 (also known as TENT5) proteins are noncanonical poly(A) polymerases (PAPs) implicated in regulating RNA stability. The regulatory mechanisms of FAM46 are poorly understood. Here, we report that the nuclear protein BCCIPalpha, but not the alternatively spliced isoform BCCIPbeta, binds FAM46 and inhibits their PAP activity. Unexpectedly, our structures of the FAM46A/BCCIPalpha and FAM46C/BCCIPalpha complexes show that, despite sharing most of the sequence and differing only at the C-terminal portion, BCCIPalpha adopts a unique structure completely different from BCCIPbeta. The distinct C-terminal segment of BCCIPalpha supports the adoption of the unique fold but does not directly interact with FAM46. The beta sheets in BCCIPalpha and FAM46 pack side by side to form an extended beta sheet. A helix-loop-helix segment in BCCIPalpha inserts into the active site cleft of FAM46, thereby inhibiting the PAP activity. Our results together show that the unique fold of BCCIPalpha underlies its interaction with and functional regulation of FAM46.
Inhibition of FAM46/TENT5 activity by BCCIPalpha adopting a unique fold.,Liu S, Chen H, Yin Y, Lu D, Gao G, Li J, Bai XC, Zhang X Sci Adv. 2023 Apr 5;9(14):eadf5583. doi: 10.1126/sciadv.adf5583. Epub 2023 Apr 5. PMID:37018411[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kuchta K, Muszewska A, Knizewski L, Steczkiewicz K, Wyrwicz LS, Pawlowski K, Rychlewski L, Ginalski K. FAM46 proteins are novel eukaryotic non-canonical poly(A) polymerases. Nucleic Acids Res. 2016 May 5;44(8):3534-48. doi: 10.1093/nar/gkw222. Epub 2016, Apr 7. PMID:27060136 doi:http://dx.doi.org/10.1093/nar/gkw222
- ↑ Mroczek S, Chlebowska J, Kulinski TM, Gewartowska O, Gruchota J, Cysewski D, Liudkovska V, Borsuk E, Nowis D, Dziembowski A. The non-canonical poly(A) polymerase FAM46C acts as an onco-suppressor in multiple myeloma. Nat Commun. 2017 Sep 20;8(1):619. doi: 10.1038/s41467-017-00578-5. PMID:28931820 doi:http://dx.doi.org/10.1038/s41467-017-00578-5
- ↑ Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10. PMID:21478870 doi:10.1038/nature09907
- ↑ Liu S, Chen H, Yin Y, Lu D, Gao G, Li J, Bai XC, Zhang X. Inhibition of FAM46/TENT5 activity by BCCIPα adopting a unique fold. Sci Adv. 2023 Apr 5;9(14):eadf5583. PMID:37018411 doi:10.1126/sciadv.adf5583
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