A 5' untranslated region containing the IRES element in the Runx1 gene is required for angiogenesis, hematopoiesis and leukemogenesis in a knock-in mouse model

Developmental Biology
Akiko NagamachiHiroaki Honda

Abstract

Although internal ribosome entry site (IRES)-mediated translation is considered important for proper cellular function, its precise biological role is not fully understood. Runx1 gene, which encodes a transcription factor implicated in hematopoiesis, angiogenesis, and leukemogenesis, contains IRES sequences in the 5' untranslated region. To clarify the roles of the IRES element in Runx1 function, we generated knock-in mice for either wild-type Runx1 or Runx1/Evi1, a Runx1 fusion protein identified in human leukemia. In both cases, native promoter-dependent transcription was retained, whereas IRES-mediated translation was eliminated. Interestingly, homozygotes expressing wild-type Runx1 deleted for the IRES element (Runx1(Delta IRES/Delta IRES)) died in utero with prominent dilatation of peripheral blood vessels due to impaired pericyte development. In addition, hematopoietic cells in the Runx1(Delta IRES/Delta IRES) fetal liver were significantly decreased, and exhibited an altered differentiation pattern, a reduced proliferative activity, and an impaired reconstitution ability. On the other hand, heterozygotes expressing Runx1/Evi1 deleted for the IRES element (Runx1(+/RE Delta IRES)) were born normally and did not show any he...Continue Reading

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Citations

Jul 16, 2015·Cancer Biology & Therapy·Christos VaklavasScott W Blume
May 27, 2015·British Journal of Haematology·Shinsuke MizutaniTsukasa Okuda
Jun 18, 2015·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·W L ChenS Y Wang
Apr 13, 2017·Diabetes·Jonathan D LamJoseph F Arboleda-Velasquez
Oct 20, 2017·BMC Developmental Biology·Sebastian NiekeIchiro Taniuchi
Aug 9, 2018·Frontiers in Physiology·Kat S Moore, Marieke von Lindern
Dec 30, 2020·The Journal of Clinical Investigation·Akiko NagamachiToshiya Inaba
Feb 5, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hatsumi NakataAtsushi Yoshiki

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