The RNA-binding protein Snd1/Tudor-SN regulates hypoxia-responsive gene expression
|Author:||Saarikettu, Juha1; Lehmusvaara, Saara2; Pesu, Marko2,3;|
1Institute of Biotechnology, HiLIFE Helsinki Institute of Life Sciences, University of Helsinki, Helsinki, Finland
2Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
3Fimlab Laboratories, Tampere University Hospital, Tampere, Finland
4Northern Finland Laboratory Centre (NordLab), Oulu, Finland
5Research Unit of Biomedicine, University of Oulu, Oulu, Finland
6Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland
7Research Centre for Integrative Physiology and Pharmacology, and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland
8Department of Immunology, Tianjin Medical University, Tianjin, P.R. China
|Online Access:||PDF Full Text (PDF, 7.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe20230913124498
John Wiley & Sons,
|Publish Date:|| 2023-09-13
Snd1 is an evolutionarily conserved RNA-binding protein implicated in several regulatory processes in gene expression including activation of transcription, mRNA splicing, and microRNA decay. Here, we have investigated the outcome of Snd1 gene deletion in the mouse. The knockout mice are viable showing no gross abnormalities apart from decreased fertility, organ and body size, and decreased number of myeloid cells concomitant with decreased expression of granule protein genes. Deletion of Snd1 affected the expression of relatively small number of genes in spleen and liver. However, mRNA expression changes in the knockout mouse liver showed high similarity to expression profile in adaptation to hypoxia. MicroRNA expression in liver showed upregulation of the hypoxia-induced microRNAs miR-96 and -182. Similar to Snd1 deletion, mimics of miR-96/182 enhanced hypoxia-responsive reporter activity. To further elucidate the function of SND1, BioID biotin proximity ligation assay was performed in HEK-293T cells to identify interacting proteins. Over 50% of the identified interactors were RNA-binding proteins, including stress granule proteins. Taken together, our results show that in normal growth conditions, Snd1 is not a critical factor for mRNA transcription in the mouse, and describe a function for Snd1 in hypoxia adaptation through negatively regulating hypoxia-related miRNAs and hypoxia-induced transcription consistent with a role as stress response regulator.
|Pages:||183 - 198|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This work was supported by the Academy of Finland (O.S 287573, M.P. 128623, M.P. 135980 and I.J. 25013080481), the Sigrid Juselius Foundation (O.S. and M.P.), the Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, Tampere Tuberculosis Foundation and the Finnish Cultural Foundation, a Marie Curie International Reintegration Grant within the 7th European Community Framework Programme (MP), Emil Aaltonen Foundation (MP), and Competitive Research Funding of the Tampere University Hospital (OS grant 9V061, MP grants 9M080, 9N056, IJ 9N018), Competitive Research Funding of the Fimlab laboratories (IJ X51409) and Finnish Medical Foundation (IJ).
© 2023 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.