{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:47:34Z","timestamp":1791272854029,"version":"4.1.0"},"reference-count":114,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM088809"],"award-info":[{"award-number":["GM088809"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HG006892"],"award-info":[{"award-number":["HG006892"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR066741"],"award-info":[{"award-number":["AR066741"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs RNA"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n                    Alternative splicing (\n                    <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\n                    ) is an important mechanism used to generate greater transcriptomic and proteomic diversity from a finite genome. Nearly all human gene transcripts are alternatively spliced and can produce protein isoforms with divergent and even antagonistic properties that impact cell functions. Many\n                    <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\n                    events are tightly regulated in a cell\u2010type or tissue\u2010specific manner, and at different developmental stages.\n                    <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\n                    is regulated by\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \u2010binding proteins, including cell\u2010 or tissue\u2010specific splicing factors. In the past few years, technological advances have defined genome\u2010wide programs of AS regulated by increasing numbers of splicing factors. These splicing regulatory networks (\n                    <jats:styled-content style=\"fixed-case\">SRNs<\/jats:styled-content>\n                    ) consist of transcripts that encode proteins that function in coordinated and related processes that impact the development and phenotypes of different cell types. As such, it is increasingly recognized that disruption of normal programs of splicing regulated by different splicing factors can lead to human diseases. We will summarize examples of diseases in which altered expression or function of splicing regulatory proteins has been implicated in human disease pathophysiology. As the role of\n                    <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\n                    continues to be unveiled in human disease and disease risk, it is hoped that further investigations into the functions of numerous splicing factors and their regulated targets will enable the development of novel therapies that are directed at specific\n                    <jats:styled-content style=\"fixed-case\">AS<\/jats:styled-content>\n                    events as well as the biological pathways they impact.\n                    <jats:italic>WIREs RNA<\/jats:italic>\n                    2015, 6:311\u2013326. doi: 10.1002\/wrna.1276\n                  <\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>RNA Processing &gt; Splicing Mechanisms<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>RNA Processing &gt; Splicing Regulation\/Alternative Splicing<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>RNA in Disease and Development &gt; RNA in Disease<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1002\/wrna.1276","type":"journal-article","created":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T07:27:14Z","timestamp":1422430034000},"page":"311-326","source":"Crossref","is-referenced-by-count":135,"title":["Functional roles of alternative splicing factors in human disease"],"prefix":"10.1002","volume":"6","author":[{"given":"Benjamin","family":"Cieply","sequence":"first","affiliation":[{"name":"Departments of Medicine (Renal) and Genetics University of Pennsylvania, Perelman School of Medicine  Philadelphia PA 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