Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.

IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabet...

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Main Authors: Hang T T Le, Alice M Sorrell, Kenneth Siddle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033140&type=printable
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author Hang T T Le
Alice M Sorrell
Kenneth Siddle
author_facet Hang T T Le
Alice M Sorrell
Kenneth Siddle
author_sort Hang T T Le
collection DOAJ
description IGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5'-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50-90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function.
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spelling doaj-art-7c75bb75adb8432d962fff1474fba3ec2025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3314010.1371/journal.pone.0033140Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.Hang T T LeAlice M SorrellKenneth SiddleIGF2BP2 is a member of a family of mRNA binding proteins that, collectively, have been shown to bind to several different mRNAs in mammalian cells, including one of the mRNAs encoding insulin-like growth factor-2. Polymorphisms in the Igf2bp2 gene are associated with risk of developing type 2 diabetes, but detailed functional characterisation of IGF2BP2 protein is lacking. By immunoblotting with C-terminally reactive antibodies we identified a novel IGF2BP2 isoform with a molecular weight of 58 kDa in both human and rodents, that is expressed at somewhat lower levels than the full-length 65 kDa protein. We demonstrated by mutagenesis that this isoform is generated by alternative translation initiation at the internal Met69. It lacks a conserved N-terminal RNA Recognition Motif (RRM) and would be predicted to differ functionally from the canonical full length isoform. We further investigated IGF2BP2 mRNA transcripts by amplification of cDNA using 5'-RACE. We identified multiple transcription start sites of the human, mouse and rat Igf2bp2 genes in a highly conserved region only 50-90 nts upstream of the major translation start site, ruling out the existence of N-terminally extended isoforms. We conclude that structural heterogeneity of IGF2BP2 protein should be taken into account when considering cellular function.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033140&type=printable
spellingShingle Hang T T Le
Alice M Sorrell
Kenneth Siddle
Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
PLoS ONE
title Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
title_full Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
title_fullStr Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
title_full_unstemmed Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
title_short Two isoforms of the mRNA binding protein IGF2BP2 are generated by alternative translational initiation.
title_sort two isoforms of the mrna binding protein igf2bp2 are generated by alternative translational initiation
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0033140&type=printable
work_keys_str_mv AT hangttle twoisoformsofthemrnabindingproteinigf2bp2aregeneratedbyalternativetranslationalinitiation
AT alicemsorrell twoisoformsofthemrnabindingproteinigf2bp2aregeneratedbyalternativetranslationalinitiation
AT kennethsiddle twoisoformsofthemrnabindingproteinigf2bp2aregeneratedbyalternativetranslationalinitiation