FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2028963450> ?p ?o ?g. }

• W2028963450 abstract "RNA splicing, the process that removes introns from pre-mRNA and links exons together to generate the fully mature messenger RNA (mRNA), is a complicated and highly regulated process. Splicing is catalyzed by the spliceosome, a large RNA-protein complex composed of several small nuclear ribonucleoprotein complexes (snRNPs) that each have a specific task during splicing. Correct splicing is important, since RNAs that retain introns or parts of introns will not be translated correctly into proteins and may even be degraded.In two studies using whole exome sequencing of myelodysplasia cases, recurrent mutations involving components of the RNA splicing machinery, including SF3B1, SRSF2, U2AF35, ZRSR2, PRPF40B, U2AF65 and SF1, have been identified.1,2 Myelodysplastic syndromes (MDS) and related disorders (myelodysplasia) are a group of myeloid neoplasms characterized by deregulated, dysplastic blood cell production and a predisposition to develop acute myeloid leukemia (AML).3 Analysis of the various mutations indicated that the mutations were not random loss-of-function mutations, but they appeared to be selected to retain structural integrity.2 Thus, rather than loss of splicing activity, which would probably lead to cell death, it is expected that the mutated splicing factors will have an altered function.How can splicing defects lead to myelodysplasia? The answer to this question is still unknown, but experiments in cell lines have provided some first indications. When expressed in HeLa cells, the mutant U2AF35 induced global abnormalities of RNA splicing, leading to increased production of transcripts having unspliced intronic sequences, and thereby activating the nonsense mediated RNA decay pathway (a surveillance pathway that degrades mRNAs that have premature stop codons).1 The biological consequences were studied in HeLa cells and mouse hematopoietic stem/progenitor cells, where a negative effect on cell proliferation and a compromised reconstitution capacity of the hematopoietic stem/progenitor cells was observed for cells expressing the U2AF35 mutants.1What are the clinical consequences of these mutations? In a follow-up study, somatic mutations of SF3B1 were identified in 150 of 533 (28 %) patients with MDS, 16 of 83 (19 %) with MDS/MPN, and only in 2 of 38 (5 %) with AML.4 The association of SF3B1 mutations with the presence of ring sideroblasts was highly significant, and the mutant gene had a positive predictive value for ring sideroblasts of almost 98 percent.4,5 In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival and lower risk of transformation to AML.4 These findings suggest that the incorporation of SF3B1 mutation analysis into the risk stratification systems might further improve risk assessment in MDS. Interestingly, SF3B1 mutations have recently also been identified in chronic lymphocytic leukemia (CLL), where the highest frequency of SF3B1 mutations was found in fludarabine-refractory cases.6 These studies suggest that mutations in splicing factors may be common in various hematologic malignancies.These data provide the first evidence that genetic alterations of splicing components can be implicated in the pathogenesis of human disease, and may lead to the development of novel therapeutic possibilities to treat myelodysplasia." @default.
• W2028963450 created "2016-06-24" @default.
• W2028963450 creator A5060184481 @default.
• W2028963450 date "2011-12-30" @default.
• W2028963450 modified "2023-10-12" @default.
• W2028963450 title "When splicing turns bad" @default.
• W2028963450 cites W2043415097 @default.
• W2028963450 cites W2073889874 @default.
• W2028963450 cites W2140419897 @default.
• W2028963450 cites W2144892629 @default.
• W2028963450 cites W2150887357 @default.
• W2028963450 cites W2154126458 @default.
• W2028963450 doi "https://doi.org/10.3324/haematol.2011.060996" @default.
• W2028963450 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3248921" @default.
• W2028963450 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22210325" @default.
• W2028963450 hasPublicationYear "2011" @default.
• W2028963450 type Work @default.
• W2028963450 sameAs 2028963450 @default.
• W2028963450 citedByCount "3" @default.
• W2028963450 countsByYear W20289634502012 @default.
• W2028963450 countsByYear W20289634502013 @default.
• W2028963450 countsByYear W20289634502017 @default.
• W2028963450 crossrefType "journal-article" @default.
• W2028963450 hasAuthorship W2028963450A5060184481 @default.
• W2028963450 hasBestOaLocation W20289634501 @default.
• W2028963450 hasConcept C104317684 @default.
• W2028963450 hasConcept C194583182 @default.
• W2028963450 hasConcept C36823959 @default.
• W2028963450 hasConcept C40000846 @default.
• W2028963450 hasConcept C42576000 @default.
• W2028963450 hasConcept C54355233 @default.
• W2028963450 hasConcept C54458228 @default.
• W2028963450 hasConcept C67705224 @default.
• W2028963450 hasConcept C68483431 @default.
• W2028963450 hasConcept C70219777 @default.
• W2028963450 hasConcept C73758832 @default.
• W2028963450 hasConcept C75934600 @default.
• W2028963450 hasConcept C86803240 @default.
• W2028963450 hasConcept C94671646 @default.
• W2028963450 hasConcept C95444343 @default.
• W2028963450 hasConceptScore W2028963450C104317684 @default.
• W2028963450 hasConceptScore W2028963450C194583182 @default.
• W2028963450 hasConceptScore W2028963450C36823959 @default.
• W2028963450 hasConceptScore W2028963450C40000846 @default.
• W2028963450 hasConceptScore W2028963450C42576000 @default.
• W2028963450 hasConceptScore W2028963450C54355233 @default.
• W2028963450 hasConceptScore W2028963450C54458228 @default.
• W2028963450 hasConceptScore W2028963450C67705224 @default.
• W2028963450 hasConceptScore W2028963450C68483431 @default.
• W2028963450 hasConceptScore W2028963450C70219777 @default.
• W2028963450 hasConceptScore W2028963450C73758832 @default.
• W2028963450 hasConceptScore W2028963450C75934600 @default.
• W2028963450 hasConceptScore W2028963450C86803240 @default.
• W2028963450 hasConceptScore W2028963450C94671646 @default.
• W2028963450 hasConceptScore W2028963450C95444343 @default.
• W2028963450 hasLocation W20289634501 @default.
• W2028963450 hasLocation W20289634502 @default.
• W2028963450 hasLocation W20289634503 @default.
• W2028963450 hasLocation W20289634504 @default.
• W2028963450 hasOpenAccess W2028963450 @default.
• W2028963450 hasPrimaryLocation W20289634501 @default.
• W2028963450 hasRelatedWork W2020577703 @default.
• W2028963450 hasRelatedWork W2045876806 @default.
• W2028963450 hasRelatedWork W2066314851 @default.
• W2028963450 hasRelatedWork W2087414058 @default.
• W2028963450 hasRelatedWork W2150371267 @default.
• W2028963450 hasRelatedWork W2167750080 @default.
• W2028963450 hasRelatedWork W2324686704 @default.
• W2028963450 hasRelatedWork W2335041518 @default.
• W2028963450 hasRelatedWork W2470492553 @default.
• W2028963450 hasRelatedWork W2491647732 @default.
• W2028963450 hasRelatedWork W2513158531 @default.
• W2028963450 hasRelatedWork W2549094383 @default.
• W2028963450 hasRelatedWork W2555600173 @default.
• W2028963450 hasRelatedWork W2568562539 @default.
• W2028963450 hasRelatedWork W2594056763 @default.
• W2028963450 hasRelatedWork W2890105668 @default.
• W2028963450 hasRelatedWork W2976145746 @default.
• W2028963450 hasRelatedWork W2999715634 @default.
• W2028963450 hasRelatedWork W3021249295 @default.
• W2028963450 hasRelatedWork W3114036715 @default.
• W2028963450 isParatext "false" @default.
• W2028963450 isRetracted "false" @default.
• W2028963450 magId "2028963450" @default.
• W2028963450 workType "article" @default.