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RNA-binding protein IGF2BP1 is required for spermatogenesis in an age-dependent manner

ABSTRACT: This study characterizes the in vivo function of RNA-binding protein IGF2BP1 during spermatogenesis, and further identifies ELAVL1 as a novel binding partner, and Lin28a mRNA as a downstream target.

ORGANISM(S): Mus musculus

PROVIDER: GSE275200 | GEO | 2024/08/24

REPOSITORIES: GEO

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RNA-binding protein IGF2BP1 is required for spermatogenesis in an age-dependent manner

Project description:Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis

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RNA-binding protein IGF2BP1 is required for spermatogenesis in an age-dependent manner

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IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [IGF2BP1 and SRF KD in ES-2 (total RNA)]

Project description:The oncofetal mRNA-binding protein IGF2BP1 and the transcriptional regulator SRF modulate gene expression in cancer. In cancer cells, we demonstrate that IGF2BP1 promotes the expression of SRF in a conserved and N6-methyladenosine (m6A) dependent manner by impairing the miRNA-directed decay of the SRF mRNA. This results in enhanced SRF-dependent transcriptional activity and promotes tumor cell growth and invasion. At the post-transcriptional level, IGF2BP1 sustains the expression of various SRF-target genes. The majority of these SRF/IGF2BP1-enhanced genes, including PDLIM7 and FOXK1, shows conserved upregulation with SRF and IGF2BP1 synthesis in cancer. PDLIM7 and FOXK1 promote tumor cell growth and were reported to enhance cell invasion. Consistently, 35 SRF/IGF2BP1-dependent genes showing conserved association with SRF and IGF2BP1 expression indicate a poor overall survival probability in ovarian, liver and lung cancer. In conclusion, these findings identify the SRF/IGF2BP1-, miRNome- and m6A-dependent control of gene expression as a conserved oncogenic driver network in cancer.

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IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [miRNA-seq]

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IGF2BP1 promotes SRF-dependent transcription in cancer in a m6A- and miRNA-dependent manner [Huh-7]

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