SRSF2 is required for mRNA splicing during spermatogenesis

Abstract Background RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Results Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also...

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Main Authors: Wen-Long Lei, Zongchang Du, Tie-Gang Meng, Ruibao Su, Yuan-Yuan Li, Wenbo Liu, Si-Min Sun, Meng-Yu Liu, Yi Hou, Chun-Hui Zhang, Yaoting Gui, Heide Schatten, Zhiming Han, Chenli Liu, Fei Sun, Zhen-Bo Wang, Wei-Ping Qian, Qing-Yuan Sun
Format: Article
Language:English
Published: BMC 2023-10-01
Series:BMC Biology
Subjects:
Online Access:https://doi.org/10.1186/s12915-023-01736-6
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author Wen-Long Lei
Zongchang Du
Tie-Gang Meng
Ruibao Su
Yuan-Yuan Li
Wenbo Liu
Si-Min Sun
Meng-Yu Liu
Yi Hou
Chun-Hui Zhang
Yaoting Gui
Heide Schatten
Zhiming Han
Chenli Liu
Fei Sun
Zhen-Bo Wang
Wei-Ping Qian
Qing-Yuan Sun
author_facet Wen-Long Lei
Zongchang Du
Tie-Gang Meng
Ruibao Su
Yuan-Yuan Li
Wenbo Liu
Si-Min Sun
Meng-Yu Liu
Yi Hou
Chun-Hui Zhang
Yaoting Gui
Heide Schatten
Zhiming Han
Chenli Liu
Fei Sun
Zhen-Bo Wang
Wei-Ping Qian
Qing-Yuan Sun
author_sort Wen-Long Lei
collection DOAJ
description Abstract Background RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Results Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Conclusions Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.
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spelling doaj.art-fbd9857c935f43368e9543d688bf703d2023-11-20T10:55:35ZengBMCBMC Biology1741-70072023-10-0121111510.1186/s12915-023-01736-6SRSF2 is required for mRNA splicing during spermatogenesisWen-Long Lei0Zongchang Du1Tie-Gang Meng2Ruibao Su3Yuan-Yuan Li4Wenbo Liu5Si-Min Sun6Meng-Yu Liu7Yi Hou8Chun-Hui Zhang9Yaoting Gui10Heide Schatten11Zhiming Han12Chenli Liu13Fei Sun14Zhen-Bo Wang15Wei-Ping Qian16Qing-Yuan Sun17Guangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, The Center of Reproductive Medicine, Peking University Shenzhen HospitalSchool of Artificial Intelligence, University of Chinese Academy of SciencesFertility Preservation Lab, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General HospitalFertility Preservation Lab, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General HospitalState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesDepartment of Obstetrics and Gynecology, Center for Reproductive Medicine/Department of Fetal Medicine and Prenatal Diagnosis/BioResource Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesGuangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, The Center of Reproductive Medicine, Peking University Shenzhen HospitalInstitute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical CenterDepartment of Veterinary Pathobiology, University of MissouriState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of SciencesDepartment of Urology & Andrology, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of SciencesGuangdong and Shenzhen Key Laboratory of Reproductive Medicine and Genetics, The Center of Reproductive Medicine, Peking University Shenzhen HospitalFertility Preservation Lab, Guangdong-Hongkong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General HospitalAbstract Background RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. Results Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. Conclusions Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.https://doi.org/10.1186/s12915-023-01736-6SRSF2Male infertilitySpermatogenesisAlternative splicingLACE-seq
spellingShingle Wen-Long Lei
Zongchang Du
Tie-Gang Meng
Ruibao Su
Yuan-Yuan Li
Wenbo Liu
Si-Min Sun
Meng-Yu Liu
Yi Hou
Chun-Hui Zhang
Yaoting Gui
Heide Schatten
Zhiming Han
Chenli Liu
Fei Sun
Zhen-Bo Wang
Wei-Ping Qian
Qing-Yuan Sun
SRSF2 is required for mRNA splicing during spermatogenesis
BMC Biology
SRSF2
Male infertility
Spermatogenesis
Alternative splicing
LACE-seq
title SRSF2 is required for mRNA splicing during spermatogenesis
title_full SRSF2 is required for mRNA splicing during spermatogenesis
title_fullStr SRSF2 is required for mRNA splicing during spermatogenesis
title_full_unstemmed SRSF2 is required for mRNA splicing during spermatogenesis
title_short SRSF2 is required for mRNA splicing during spermatogenesis
title_sort srsf2 is required for mrna splicing during spermatogenesis
topic SRSF2
Male infertility
Spermatogenesis
Alternative splicing
LACE-seq
url https://doi.org/10.1186/s12915-023-01736-6
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