Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay

Yifen Shen; Le Zhang; Tao Yang; Xiaosong Li; Chao Liu; Hongmei Li; Yanping Hu; Hao Shen; Hua Li; Yuriy L Orlov; Shasha Zhou; Yihang Shen

doi:10.1007/s12035-024-04450-8

Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay

Mol Neurobiol. 2024 Sep 5. doi: 10.1007/s12035-024-04450-8. Online ahead of print.

Authors

Yifen Shen^#¹, Le Zhang^#^{2

3}, Tao Yang^#⁴, Xiaosong Li⁵, Chao Liu¹, Hongmei Li⁶, Yanping Hu⁷, Hao Shen⁸, Hua Li⁹, Yuriy L Orlov^{10

11}, Shasha Zhou¹², Yihang Shen¹³

Affiliations

¹ Central Laboratory, Suzhou Bay Clinical College, Xuzhou Medical University, Suzhou Ninth People's Hospital, Soochow University, Suzhou, 215200, Jiangsu, China.
² Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, Suzhou, 215009, Jiangsu, China.
³ Bio-ID Center, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁴ Department of Medical Cosmetology, Suzhou Ninth People's Hospital, Soochow University, Suzhou, 215200, Jiangsu, China.
⁵ Department of Anorectal Surgery, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China.
⁶ Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200023, China.
⁷ Department of Molecular Pathology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, 450008, Henan, China.
⁸ Clinical Laboratory, Suzhou Ninth People's Hospital, Suzhou, 215200, Jiangsu, China.
⁹ Jiangsu Province Engineering Research Center of Molecular Target Therapy and Companion Diagnostics in Oncology, Suzhou Vocational Health College, Suzhou, 215009, Jiangsu, China. kaikaixinxin@sjtu.edu.cn.
¹⁰ The Digital Health Center, Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991, Russia. orlov@d-health.institute.
¹¹ Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. orlov@d-health.institute.
¹² Department of Endocrinology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200040, China. zhoushasha@sjtu.edu.cn.
¹³ Central Laboratory, Suzhou Bay Clinical College, Xuzhou Medical University, Suzhou Ninth People's Hospital, Soochow University, Suzhou, 215200, Jiangsu, China. devbrother@sjtu.edu.cn.

^# Contributed equally.

PMID: 39235646
DOI: 10.1007/s12035-024-04450-8

Abstract

Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.

Keywords: ARC; Hypothalamus; IGF2BP2; Monosome; Puberty; Ribosome; Translation regulation.

Abstract

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