Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress

MicroRNAs (miRNAs) are small non-coding RNAs that have well-characterized roles in cytoplasmic gene regulation, where they act by binding to mRNA transcripts and inhibiting their translation (i.e. post-transcriptional gene silencing, PTGS). However, miRNAs have also been implicated in transcriptiona...

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Main Authors: Turunen, T, Roberts, T, Laitinen, P, Väänänen, M, Korhonen, P, Malm, T, Ylä-Herttuala, S, Turunen, M
Format: Journal article
Language:English
Published: Nature Research 2019
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author Turunen, T
Roberts, T
Laitinen, P
Väänänen, M
Korhonen, P
Malm, T
Ylä-Herttuala, S
Turunen, M
author_facet Turunen, T
Roberts, T
Laitinen, P
Väänänen, M
Korhonen, P
Malm, T
Ylä-Herttuala, S
Turunen, M
author_sort Turunen, T
collection OXFORD
description MicroRNAs (miRNAs) are small non-coding RNAs that have well-characterized roles in cytoplasmic gene regulation, where they act by binding to mRNA transcripts and inhibiting their translation (i.e. post-transcriptional gene silencing, PTGS). However, miRNAs have also been implicated in transcriptional gene regulation and alternative splicing, events that are restricted to the cell nucleus. Here we performed nuclear-cytoplasmic fractionation in a mouse endothelial cell line and characterized the localization of miRNAs in response to hypoxia using small RNA sequencing. A highly diverse population of abundant miRNA species was detected in the nucleus, of which the majority (56%) was found to be preferentially localized in one compartment or the other. Induction of hypoxia resulted in changes in miRNA levels in both nuclear and cytoplasmic compartments, with the majority of changes being restricted to one location and not the other. Notably, the classical hypoxamiR (miR-210-3p) was highly up-regulated in the nuclear compartment after hypoxic stimulus. These findings reveal a previously unappreciated level of molecular complexity in the physiological response occurring in ischemic tissue. Furthermore, widespread differential miRNA expression in the nucleus strongly suggests that these small RNAs are likely to perform extensive nuclear regulatory functions in the general case.
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spelling oxford-uuid:d0333d03-cfb6-4bef-984e-869f27d43d1c2022-03-27T07:48:21ZChanges in nuclear and cytoplasmic microRNA distribution in response to hypoxic stressJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0333d03-cfb6-4bef-984e-869f27d43d1cEnglishSymplectic Elements at OxfordNature Research2019Turunen, TRoberts, TLaitinen, PVäänänen, MKorhonen, PMalm, TYlä-Herttuala, STurunen, MMicroRNAs (miRNAs) are small non-coding RNAs that have well-characterized roles in cytoplasmic gene regulation, where they act by binding to mRNA transcripts and inhibiting their translation (i.e. post-transcriptional gene silencing, PTGS). However, miRNAs have also been implicated in transcriptional gene regulation and alternative splicing, events that are restricted to the cell nucleus. Here we performed nuclear-cytoplasmic fractionation in a mouse endothelial cell line and characterized the localization of miRNAs in response to hypoxia using small RNA sequencing. A highly diverse population of abundant miRNA species was detected in the nucleus, of which the majority (56%) was found to be preferentially localized in one compartment or the other. Induction of hypoxia resulted in changes in miRNA levels in both nuclear and cytoplasmic compartments, with the majority of changes being restricted to one location and not the other. Notably, the classical hypoxamiR (miR-210-3p) was highly up-regulated in the nuclear compartment after hypoxic stimulus. These findings reveal a previously unappreciated level of molecular complexity in the physiological response occurring in ischemic tissue. Furthermore, widespread differential miRNA expression in the nucleus strongly suggests that these small RNAs are likely to perform extensive nuclear regulatory functions in the general case.
spellingShingle Turunen, T
Roberts, T
Laitinen, P
Väänänen, M
Korhonen, P
Malm, T
Ylä-Herttuala, S
Turunen, M
Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title_full Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title_fullStr Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title_full_unstemmed Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title_short Changes in nuclear and cytoplasmic microRNA distribution in response to hypoxic stress
title_sort changes in nuclear and cytoplasmic microrna distribution in response to hypoxic stress
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