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Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia\/amyotrophic lateral sclerosis (FTD\/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology.<\/jats:p>","DOI":"10.1007\/s00439-021-02409-6","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T05:35:04Z","timestamp":1639546504000},"page":"31-47","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Differential fates of introns in gene expression due to global alternative splicing"],"prefix":"10.1007","volume":"141","author":[{"given":"Anjani","family":"Kumari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saam","family":"Sedehizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John David","family":"Brook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Kozlowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-2407","authenticated-orcid":false,"given":"Marzena","family":"Wojciechowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"2409_CR1","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1038\/ng.2434","volume":"44","author":"M Armakola","year":"2012","unstructured":"Armakola M, Higgins MJ, Figley MD et al (2012) Inhibition of RNA lariat debranching enzyme suppresses TDP-43 toxicity in ALS disease models. 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