Pre-mRNA splicing is performed by the spliceosome, a dynamic macromolecular complex consisting of five small uridine-rich ribonucleoprotein complexes (the U1, U2, U4, U5, and U6 snRNPs) and numerous auxiliary splicing factors. A plethora of human disorders are caused by genetic variants affecting the function and/or expression of splicing factors, including the core snRNP proteins. Variants in the genes encoding proteins of the U5 snRNP cause two distinct and tissue-specific human disease phenotypes – variants in PRPF6, PRPF8, and SNRP200 are associated with retinitis pigmentosa (RP), while variants in EFTUD2 and TXNL4A cause the craniofacial disorders mandibulofacial dysostosis Guion-Almeida type (MFDGA) and Burn-McKeown syndrome (BMKS), respectively. Furthermore, recurrent somatic mutations or changes in the expression levels of a number of U5 snRNP proteins (PRPF6, PRPF8, EFTUD2, DDX23, and SNRNP40) have been associated with human cancers. How and why variants in ubiquitously expressed spliceosome proteins required for pre-mRNA splicing in all human cells result in tissue-restricted disease phenotypes is not clear. Additionally, why variants in different, yet interacting, proteins making up the same core spliceosome snRNP result in completely distinct disease outcomes – RP, craniofacial defects or cancer – is unclear. In this review, we define the roles of different U5 snRNP proteins in RP, craniofacial disorders and cancer, including how disease-associated genetic variants affect pre-mRNA splicing and the proposed disease mechanisms. We then propose potential hypotheses for how U5 snRNP variants cause tissue specificity resulting in the restricted and distinct human disorders.

Journal of Blood Disorders & Transfusion (ISSN: 2155-9864// NLM I'D: 101630198) is a peer reviewed and open access journal aimed to publish most interesting and complete reliable source of information on current development and advanced research findings in the mode of original articles, review articles, case reports, short communications, etc. in all areas of the field and making them freely available through online without any restrictions or any other subscriptions to researchers worldwide.

Journal of Blood Disorders & Transfusion is an scholarly journal that focuses on all aspects of molecular genetics, pathophysiology and epidemiology as well as prevention, diagnosis, and management of blood disorders with current state of research in the field of transfusion medicine, hematology, hemato-oncology, pediatric hematology, laboratory hematology, neuropathy, blood donors, thalassemia, bone marrow transplantation, anti-HBc, haemodilution, hemodialysis, blood stem cell, blood disorders, Rh factor, blood cancer, platelet disorders, hemolytic anemia etc.

Submit manuscript at https://www.longdom.org/submissions/blood-disorders-transfusion.html or send us an email attachment to the Editorial Office at editor.jbdt@clinicalinsight.org

Thank you, and Regards,
John Robert
Journal of Blood Disorders & Transfusion
ISSN: 2155-9864| NLM ID: 101630198