Grsf1, also known as G-rich RNA sequence-binding factor 1, belongs to the heterogeneous nuclear ribonucleoproteins F/H (hnRNP F/H) subfamily. It is a mitochondrial RNA-binding protein widely distributed in eukaryotic cells, present in the nucleus, cytoplasm, and mitochondria. Grsf1 is implicated in multiple physiological processes such as embryogenesis, erythropoiesis, redox homeostasis, and RNA metabolism [5].

In aging-related studies, Grsf1 deficiency has significant impacts. In skeletal muscle, Grsf1-specific ablation in mice (Grsf1cKO) led to reduced muscle endurance in aged mice, with changes in mRNAs related to mitochondrial function, inflammation, and ion transport [4]. In ovarian granulosa cells, decreased Grsf1 expression exacerbated mitochondrial dysfunction, elevated reactive oxygen species, and impaired ATP production [3]. Also, Grsf1 levels decline in senescent cells, and its reduction causes mitochondrial stress, DNA damage, and cell senescence-associated phenotypes like increased SA-β-gal activity and IL6 secretion [1]. Moreover, Grsf1 antagonizes age-associated hypercoagulability by modulating fibrinogen mRNA stability, as its overexpression in old mice liver decreased fibrinogen plasma level and hypercoagulability, while knockdown in young mice liver had the opposite effects [2].

In conclusion, Grsf1 plays essential roles in maintaining mitochondrial function, redox homeostasis, and regulating cellular senescence and blood coagulation. Studies using Grsf1 KO/CKO mouse models have revealed its significance in age-related physiological decline and associated diseases, providing insights into potential therapeutic targets for age-related disorders.

References:

1. Noh, Ji Heon, Kim, Kyoung Mi, Idda, M Laura, Abdelmohsen, Kotb, Gorospe, Myriam. . GRSF1 suppresses cell senescence. In Aging, 10, 1856-1866. doi:10.18632/aging.101516. https://pubmed.ncbi.nlm.nih.gov/30086537/

2. Liu, Doudou, Xu, Chenzhong, Gong, Ze, Kong, Wei, Chen, Jun. 2023. GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability. In Cell death & disease, 14, 717. doi:10.1038/s41419-023-06242-9. https://pubmed.ncbi.nlm.nih.gov/37923734/

3. Wen, Canxin, Jiang, Linlin, Pan, Ping, Ou, Songbang, Li, Yu. 2024. GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells. In Reproduction (Cambridge, England), 168, . doi:10.1530/REP-24-0015. https://pubmed.ncbi.nlm.nih.gov/38819377/

4. Driscoll, Riley K, Krasniewski, Linda K, Cockey, Samuel G, Cui, Chang-Yi, Gorospe, Myriam. 2021. GRSF1 deficiency in skeletal muscle reduces endurance in aged mice. In Aging, 13, 14557-14570. doi:10.18632/aging.203151. https://pubmed.ncbi.nlm.nih.gov/34078750/

5. Dumoulin, Bernhard, Ufer, Christoph, Kuhn, Hartmut, Sofi, Sajad. 2021. Expression Regulation, Protein Chemistry and Functional Biology of the Guanine-Rich Sequence Binding Factor 1 (GRSF1). In Journal of molecular biology, 433, 166922. doi:10.1016/j.jmb.2021.166922. https://pubmed.ncbi.nlm.nih.gov/33713675/