{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:00:23Z","timestamp":1774548023609,"version":"3.50.1"},"reference-count":160,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T00:00:00Z","timestamp":1607558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/MULTI\/04046\/2019"],"award-info":[{"award-number":["UID\/MULTI\/04046\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/PD\/BD\/142898\/2018"],"award-info":[{"award-number":["SFRH\/PD\/BD\/142898\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alternative splicing (AS) of precursor mRNA (pre-mRNA) is a cellular post-transcriptional process that generates protein isoform diversity. Nonsense-mediated RNA decay (NMD) is an mRNA surveillance pathway that recognizes and selectively degrades transcripts containing premature translation-termination codons (PTCs), thereby preventing the production of truncated proteins. Nevertheless, NMD also fine-tunes the gene expression of physiological mRNAs encoding full-length proteins. Interestingly, around one third of all AS events results in PTC-containing transcripts that undergo NMD. Numerous studies have reported a coordinated action between AS and NMD, in order to regulate the expression of several genes, especially those coding for RNA-binding proteins (RBPs). This coupling of AS to NMD (AS-NMD) is considered a gene expression tool that controls the ratio of productive to unproductive mRNA isoforms, ultimately degrading PTC-containing non-functional mRNAs. In this review, we focus on the mechanisms underlying AS-NMD, and how this regulatory process is able to control the homeostatic expression of numerous RBPs, including splicing factors, through auto- and cross-regulatory feedback loops. Furthermore, we discuss the importance of AS-NMD in the regulation of biological processes, such as cell differentiation. Finally, we analyze interesting recent data on the relevance of AS-NMD to human health, covering its potential roles in cancer and other disorders.<\/jats:p>","DOI":"10.3390\/ijms21249424","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T08:59:34Z","timestamp":1607590774000},"page":"9424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Perspective in Alternative Splicing Coupled to Nonsense-Mediated mRNA Decay"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5323-8608","authenticated-orcid":false,"given":"Juan F.","family":"Garc\u00eda-Moreno","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, 1649-016 Lisboa, Portugal"},{"name":"Faculty of Science, BioISI\u2014Biosystems and Integrative Sciences Institute, University of Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Lu\u00edsa","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, 1649-016 Lisboa, Portugal"},{"name":"Faculty of Science, BioISI\u2014Biosystems and Integrative Sciences Institute, University of Lisboa, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"ref_1","unstructured":"Burge, C.S., Tuschl, T., and Sharp, P.A. 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