More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation

Luco, Reini F.; Misteli, Tom

doi:10.1016/j.gde.2011.03.004

Cited by 113 publications

(74 citation statements)

References 49 publications

(56 reference statements)

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“…32,33 POTENTIAL CONSEQUENCES OF SPLICEOSOME MUTATIONS Splicing is often tightly coupled with transcription 34,35 and recent work suggests that alternative splicing might be affected by chromatin structure and histone modification. 35,36 Some of these effects might involve direct recruitment of splice factors by chromatin mark readers, as has been shown for MRG15 (also known as MORF4L1) binding to H3K36me3 and recruitment of the polypyrimidine tract-binding protein to the nascent mRNA. 37 The lack of SF3B1 may impair PRC1 function 18 and the SPT3-TAFII31-GCN5L acetylase complex may also interact with splice factors.…”

Section: Sf3b1 Mutationsmentioning

confidence: 99%

“…In aggregate, these observations add to the description on the role of the loss of the ribosomal protein gene RPS14 in the pathogenesis of the dyserythropoiesis in MDS associated with 5q À 49 and also the emerging role of non-coding RNA in the regulation of splicing. 36 The potential value of these mutations as a drug target is currently being explored. 50…”

Section: Sf3b1 Mutationsmentioning

confidence: 99%

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Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies

et al. 2012

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Spliceosome mutations represent a new generation of acquired genetic alterations that affect both myeloid and lymphoid malignancies. A substantial proportion of patients with myelodysplastic syndromes (MDSs) or chronic lymphocytic leukemia (CLL) harbor such mutations, which are often missense in type. Genotype-phenotype associations have been demonstrated for one of these mutations, SF3B1, with ring sideroblasts in MDS and 11q22 deletions in CLL. Spliceosome mutations might result in defective spliceosome assembly, deregulated global mRNA splicing, nuclear-cytoplasm export and altered expression of multiple genes. Such mutations are infrequent in other lymphomas, which instead display a separate group of novel mutations involving genes whose products are believed to affect histone acetylation and methylation and chromatin structure (for example, EZH2 and MLL2). On the other hand, some mutations (for example, NOTCH1) occur in both CLL and other immature and mature lymphoid malignancies. In the current review, we discuss potential mechanisms of cell transformation associated with spliceosome mutations, touch upon the increasing evidence regarding the clonal involvement of hematopoietic stem cells in some cases of otherwise mature lymphoid disorders and summarize recent information on recently described mutations in lymphomas. Leukemia (2012Leukemia ( ) 26, 2027Leukemia ( -2031 doi:10.1038/leu.2012 Keywords: CLL; MDS; mutations; spliceosome INTRODUCTIONIn a series of recently published work, the coding sequences of the DNA obtained from mononuclear cells of the bone marrow of patients with myelodysplastic syndromes (MDSs) were compared with presumably germline DNA (T lymphocytes or buccal swab). [1][2][3] The results have included identification of approximately 10 acquired mutations per patient sample and confirmation of the frequency of previously recognized mutations. 1 More importantly, the particular studies revealed the existence of mutations in genes whose products are involved in controlling the mechanism of splicing of pre-messenger RNA. Such mutations were mutually exclusive and were detected in 45-85% of patients with MDS; 1 the majority constituted missense mutations located in restricted regions of proteins.A similar analysis was conducted in chronic lymphocytic leukemia (CLL) where DNA from tumor cells (CD19 þ and CD5 þ lymphocytes) was compared with that of non-tumor cells (granulocytes or fibroblasts). [4][5][6][7] In addition to genes already known to be mutated in this disease, such as TP53 and ATM, 11 genes were found to be recurrently affected. 4,6 The pathway analyses predicted that these mutations affected DNA damage repair and cell cycle, the Wnt, NOTCH1 and inflammatory/TLR signaling pathways, and, as was the case in MDS, control of splicing mechanisms. 4 The common novel observation, from the above-mentioned studies, in both MDS and CLL, was the identification of mutations in genes whose products are involved in the control of RNA splicing. 8 The involvement of oncogenes in RNA processing h...

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Section: Sf3b1 Mutationsmentioning

confidence: 99%

Section: Sf3b1 Mutationsmentioning

confidence: 99%

Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies

et al. 2012

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“…Clustering analyses have identified various histone codes, including bivalent promoters (Bernstein et al, 2006), poised enhancers (Creyghton et al, 2010;Rada-Iglesias and Wysocka, 2011), and alternative splicing (Luco et al, 2010;Luco and Misteli, 2011). Computational approaches have been applied to FIG.…”

Section: Stationary Wavelet Entropy-based Clustering Approachmentioning

confidence: 99%

A Stationary Wavelet Entropy-Based Clustering Approach Accurately Predicts Gene Expression

Nguyen

Choi

et al. 2015

Journal of Computational Biology

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Studying epigenetic landscapes is important to understand the condition for gene regulation. Clustering is a useful approach to study epigenetic landscapes by grouping genes based on their epigenetic conditions. However, classical clustering approaches that often use a representative value of the signals in a fixed-sized window do not fully use the information written in the epigenetic landscapes. Clustering approaches to maximize the information of the epigenetic signals are necessary for better understanding gene regulatory environments. For effective clustering of multidimensional epigenetic signals, we developed a method called Dewer, which uses the entropy of stationary wavelet of epigenetic signals inside enriched regions for gene clustering. Interestingly, the gene expression levels were highly correlated with the entropy levels of epigenetic signals. Dewer separates genes better than a windowbased approach in the assessment using gene expression and achieved a correlation coefficient above 0.9 without using any training procedure. Our results show that the changes of the epigenetic signals are useful to study gene regulation.

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“…L e s m u t a t i o n s affectant l'épissage pourraient également entraîner une variation soit de l'efficacité de la transcription en amont, soit de la cinétique de l'export vers le cytoplasme en aval. Les vitesses de transcription, d'épissage et de transport vers le cytoplasme sont liées et influencent la structure chromatinienne [16]. Schématiquement, un ralentissement (ou une accélération) de ces processus pourrait aboutir à la fermeture (ou à l'ouverture) de la chromatine indépendamment de la régulation normale, et donc à des anomalies de la différenciation cellulaire.…”

Section: Nouveaux Gènes Impliqués Dans Les Llc Et Les Smd : Quels Ensunclassified

Mutations des gènes impliqués dans l’épissage dans les hémopathies malignes humaines

et al. 2012

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More than a splicing code: integrating the role of RNA, chromatin and non-coding RNA in alternative splicing regulation

Cited by 113 publications

References 49 publications

Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies

Spliceosome and other novel mutations in chronic lymphocytic leukemia and myeloid malignancies

A Stationary Wavelet Entropy-Based Clustering Approach Accurately Predicts Gene Expression

Mutations des gènes impliqués dans l’épissage dans les hémopathies malignes humaines

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