Matches in SemOpenAlex for { <https://semopenalex.org/work/W3202860293> ?p ?o ?g. }
- W3202860293 abstract "Abstract Introns of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes." @default.
- W3202860293 created "2021-10-11" @default.
- W3202860293 creator A5010583901 @default.
- W3202860293 creator A5016435797 @default.
- W3202860293 creator A5023735920 @default.
- W3202860293 creator A5032625076 @default.
- W3202860293 creator A5040931016 @default.
- W3202860293 creator A5041510232 @default.
- W3202860293 creator A5042084987 @default.
- W3202860293 creator A5047756866 @default.
- W3202860293 creator A5057265629 @default.
- W3202860293 creator A5059124944 @default.
- W3202860293 creator A5062543388 @default.
- W3202860293 creator A5063790056 @default.
- W3202860293 creator A5080775929 @default.
- W3202860293 creator A5087568097 @default.
- W3202860293 date "2021-09-28" @default.
- W3202860293 modified "2023-10-17" @default.
- W3202860293 title "Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia" @default.
- W3202860293 cites W1486656921 @default.
- W3202860293 cites W1487850295 @default.
- W3202860293 cites W1547570854 @default.
- W3202860293 cites W1604177959 @default.
- W3202860293 cites W1861739715 @default.
- W3202860293 cites W1966973232 @default.
- W3202860293 cites W1967732081 @default.
- W3202860293 cites W1968832089 @default.
- W3202860293 cites W1968950496 @default.
- W3202860293 cites W1970997159 @default.
- W3202860293 cites W1972931607 @default.
- W3202860293 cites W1974275894 @default.
- W3202860293 cites W1978850887 @default.
- W3202860293 cites W1979130028 @default.
- W3202860293 cites W1983859619 @default.
- W3202860293 cites W1990786456 @default.
- W3202860293 cites W1991366673 @default.
- W3202860293 cites W1993635206 @default.
- W3202860293 cites W1995006714 @default.
- W3202860293 cites W1997529651 @default.
- W3202860293 cites W2000106654 @default.
- W3202860293 cites W2001130038 @default.
- W3202860293 cites W2001147604 @default.
- W3202860293 cites W2001394720 @default.
- W3202860293 cites W2019522436 @default.
- W3202860293 cites W2021035007 @default.
- W3202860293 cites W2022862766 @default.
- W3202860293 cites W2026920658 @default.
- W3202860293 cites W2027980794 @default.
- W3202860293 cites W2031989207 @default.
- W3202860293 cites W2032872362 @default.
- W3202860293 cites W2049424828 @default.
- W3202860293 cites W2049951186 @default.
- W3202860293 cites W2051698639 @default.
- W3202860293 cites W2052418918 @default.
- W3202860293 cites W2054622868 @default.
- W3202860293 cites W2055218251 @default.
- W3202860293 cites W2055639102 @default.
- W3202860293 cites W2059846060 @default.
- W3202860293 cites W2062575193 @default.
- W3202860293 cites W2064236156 @default.
- W3202860293 cites W2066011752 @default.
- W3202860293 cites W2068722030 @default.
- W3202860293 cites W2097461905 @default.
- W3202860293 cites W2098644602 @default.
- W3202860293 cites W2099870853 @default.
- W3202860293 cites W2106984490 @default.
- W3202860293 cites W2108785432 @default.
- W3202860293 cites W2109003323 @default.
- W3202860293 cites W2119632767 @default.
- W3202860293 cites W2120772351 @default.
- W3202860293 cites W2121919944 @default.
- W3202860293 cites W2124026197 @default.
- W3202860293 cites W2127322768 @default.
- W3202860293 cites W2130241868 @default.
- W3202860293 cites W2134749398 @default.
- W3202860293 cites W2139657437 @default.
- W3202860293 cites W2142584500 @default.
- W3202860293 cites W2145067337 @default.
- W3202860293 cites W2151621038 @default.
- W3202860293 cites W2154714625 @default.
- W3202860293 cites W2155765704 @default.
- W3202860293 cites W2158228504 @default.
- W3202860293 cites W2159800234 @default.
- W3202860293 cites W2163341755 @default.
- W3202860293 cites W2168974130 @default.
- W3202860293 cites W2180229411 @default.
- W3202860293 cites W2188222158 @default.
- W3202860293 cites W2223836536 @default.
- W3202860293 cites W2318823565 @default.
- W3202860293 cites W2344664973 @default.
- W3202860293 cites W2418276263 @default.
- W3202860293 cites W2471608817 @default.
- W3202860293 cites W2610435739 @default.
- W3202860293 cites W2616018166 @default.
- W3202860293 cites W2742715352 @default.
- W3202860293 cites W2751076435 @default.
- W3202860293 cites W2766187665 @default.
- W3202860293 cites W2783257073 @default.
- W3202860293 cites W2808706850 @default.
- W3202860293 cites W2914004759 @default.