To date, only mutations in the splicing factor RNA-binding motif protein 20 (RBM20) have been causally linked to heart disease. RNA splicing is an important aspect of gene regulation in many organisms. However, until now, their role in Alzheimer’s disease was not studied in great detail,” Shulman said. RNA mis-splicing in disease. A current model of the disease process in DM is that interaction of CUG exp or CCUG exp RNA with binding proteins leads to abnormal regulation of alternative splicing for a selected group of pre-mRNAs (19, 20). If this process is not highly regulated and accurate, it leads to mis-splicing events, which may result in proteins with altered function. Close mobile search navigation. Alternative splicing of pre-mRNA increases genetic diversity, and recent studies estimate that most human multiexon genes are alternatively spliced. Marina M. Scotti and Maurice S. Sw anson. Defects at the level of the pre-mRNA splicing process represent a major cause of human disease. Genetic variation in proteins that regulate splicing has been predicted to result in trans-acting modification of disease severity for splice-site mutations (1, 2).With the use of the mouse as a model, we describe here an example of genetic interaction between a putative splicing factor and a splice-site mutation in a … A new NIA-funded study finds that changes in a process called RNA splicing interact with specific Alzheimer’s genes and may contribute to functional deficits in the Alzheimer’s brain. The study, published in the November Nature Genetics , provides new insights into the molecular process behind the disease. It could be that mutations in splicing factors are severe and embryonically lethal. Volume 2, Issue 9-10 RNA splicing is a major underlying factor that links mutations to complex traits and diseases, according to an exhaustive analysis of gene expression in … “Alterations in RNA splicing are known to be involved in the development of certain neurodegenerative conditions, such as spinal muscular atrophy and amyotrophic lateral sclerosis. RNA splicing is a major underlying factor that links mutations to complex traits and diseases, according to an exhaustive analysis of gene expression in whole genome and cell line data. Mutations in cis-acting splicing elements or its regulatory proteins have been shown to be involved in human diseases. Article navigation. About 10% of human disease mutations alter pre-mRNA splice sites. Abstract | The human transcriptome is composed of a vast RNA population that under goes . Unlike DM, where specific mis-splicing events have been linked to distinct pathological consequences (e.g., myotonia due to aberrant inclusion of CLCN1 exon 7a), it is not clear if FXTAS is a developmental splicing disease. 76 – 78 The lack of splicing factors in the list of heart disease–causing genes could have multiple explanations. Splicing of RNA is regulated by complicated mechanisms involving numerous RNA-binding proteins and the intricate network of interactions among them. The approximately 50 RNA-binding proteins shown to regulate alternative splicing are a small fraction of the more than 650 RNA-binding proteins encoded by the human genome 5, 53, and a growing number of alternative splicing regulators has been linked with various human diseases. However, the specific proteins mediating these effects have been a topic of debate. 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