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Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing

miRNAs are generally classified as “intergenic” or “intronic” based upon their genomic location. Intergenic miRNAs are known to be transcribed as independent transcription units, while intronic miRNAs are believed to be processed from the introns of their hosting transcription units and hence share...

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Autores principales: Ramalingam, Pradeep, Palanichamy, Jayanth Kumar, Singh, Anand, Das, Prerna, Bhagat, Mohita, Kassab, Muzaffer Ahmad, Sinha, Subrata, Chattopadhyay, Parthaprasad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866646/
https://www.ncbi.nlm.nih.gov/pubmed/24226766
http://dx.doi.org/10.1261/rna.041814.113
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author Ramalingam, Pradeep
Palanichamy, Jayanth Kumar
Singh, Anand
Das, Prerna
Bhagat, Mohita
Kassab, Muzaffer Ahmad
Sinha, Subrata
Chattopadhyay, Parthaprasad
author_facet Ramalingam, Pradeep
Palanichamy, Jayanth Kumar
Singh, Anand
Das, Prerna
Bhagat, Mohita
Kassab, Muzaffer Ahmad
Sinha, Subrata
Chattopadhyay, Parthaprasad
author_sort Ramalingam, Pradeep
collection PubMed
description miRNAs are generally classified as “intergenic” or “intronic” based upon their genomic location. Intergenic miRNAs are known to be transcribed as independent transcription units, while intronic miRNAs are believed to be processed from the introns of their hosting transcription units and hence share common regulatory mechanisms and expression patterns with its host gene. Recent reports in the literature suggest that some intronic miRNAs, which do not show concordance in expression with their respective host genes, might be transcribed and regulated as independent transcription units. However, there is no direct evidence for the existence of independently transcribed intronic miRNA in humans to date. We have characterized the full-length primary transcripts (pri-miRNAs) of three human intronic miRNAs—miR 106b, miR 93, and miR 24-1—by RNA ligase-mediated RACE and show that human intronic miRNA can indeed be transcribed as independent transcription units. Also, clustered miRNAs are generally believed to arise from a common primary transcript and are expected to have similar expression profiles. However, we have identified several novel alternatively spliced transcripts by RT-PCR, each of which harbors a single pre-miRNA from a cluster of closely located intronic miRNAs. We show that these transcripts represent unique pri-miRNAs for each of these clustered miRNAs. We also report the identification of conserved splice acceptor signals which are responsible for maturation of these novel splice variants. Our results suggest that alternative splicing might play a role in uncoupling the expression of clustered miRNAs from each other, which otherwise are generally believed to be co-transcribed and co-expressed.
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spelling pubmed-38666462015-01-01 Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing Ramalingam, Pradeep Palanichamy, Jayanth Kumar Singh, Anand Das, Prerna Bhagat, Mohita Kassab, Muzaffer Ahmad Sinha, Subrata Chattopadhyay, Parthaprasad RNA Articles miRNAs are generally classified as “intergenic” or “intronic” based upon their genomic location. Intergenic miRNAs are known to be transcribed as independent transcription units, while intronic miRNAs are believed to be processed from the introns of their hosting transcription units and hence share common regulatory mechanisms and expression patterns with its host gene. Recent reports in the literature suggest that some intronic miRNAs, which do not show concordance in expression with their respective host genes, might be transcribed and regulated as independent transcription units. However, there is no direct evidence for the existence of independently transcribed intronic miRNA in humans to date. We have characterized the full-length primary transcripts (pri-miRNAs) of three human intronic miRNAs—miR 106b, miR 93, and miR 24-1—by RNA ligase-mediated RACE and show that human intronic miRNA can indeed be transcribed as independent transcription units. Also, clustered miRNAs are generally believed to arise from a common primary transcript and are expected to have similar expression profiles. However, we have identified several novel alternatively spliced transcripts by RT-PCR, each of which harbors a single pre-miRNA from a cluster of closely located intronic miRNAs. We show that these transcripts represent unique pri-miRNAs for each of these clustered miRNAs. We also report the identification of conserved splice acceptor signals which are responsible for maturation of these novel splice variants. Our results suggest that alternative splicing might play a role in uncoupling the expression of clustered miRNAs from each other, which otherwise are generally believed to be co-transcribed and co-expressed. Cold Spring Harbor Laboratory Press 2014-01 /pmc/articles/PMC3866646/ /pubmed/24226766 http://dx.doi.org/10.1261/rna.041814.113 Text en © 2013 Ramalingam et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Articles
Ramalingam, Pradeep
Palanichamy, Jayanth Kumar
Singh, Anand
Das, Prerna
Bhagat, Mohita
Kassab, Muzaffer Ahmad
Sinha, Subrata
Chattopadhyay, Parthaprasad
Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title_full Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title_fullStr Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title_full_unstemmed Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title_short Biogenesis of intronic miRNAs located in clusters by independent transcription and alternative splicing
title_sort biogenesis of intronic mirnas located in clusters by independent transcription and alternative splicing
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866646/
https://www.ncbi.nlm.nih.gov/pubmed/24226766
http://dx.doi.org/10.1261/rna.041814.113
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