RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation
Abstract Background Omics technologies are widely applied in assisted reproductive technology (ART), such as embryo selection, investigation of infertility causes, and mechanisms underlying reproductive cell development. While RNAomics has shown great potential in investigating the physiology and pa...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | BMC Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12915-025-02250-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850242948071948288 |
|---|---|
| author | Huan Yao Danru Zhang Haixia Jin Yanjie Guo Yan Liu Shengnan Wang Tong Li Shenli Yuan Gang Lu Yingpu Sun |
| author_facet | Huan Yao Danru Zhang Haixia Jin Yanjie Guo Yan Liu Shengnan Wang Tong Li Shenli Yuan Gang Lu Yingpu Sun |
| author_sort | Huan Yao |
| collection | DOAJ |
| description | Abstract Background Omics technologies are widely applied in assisted reproductive technology (ART), such as embryo selection, investigation of infertility causes, and mechanisms underlying reproductive cell development. While RNAomics has shown great potential in investigating the physiology and pathology in female reproductive system, its applications are still not fully developed. More studies on epitranscriptomic regulation mechanisms and novel sequencing methods are needed to advance the field. Results Here, we developed a method named Cap to Tail sequencing application (C2T-APP) and simultaneously characterized the m7G cap, poly(A) tail structure, and gene expression level for the intact RNA molecules in single cells. C2T-APP distinguished the N6, 2′-O-dimethyladenosine modification (m6Am) from N 6-methyladenosine (m6A) modification with our published single-cell m6A sequencing (scm6A-seq) data. During oocyte maturation, we found a positive correlation of m7G and m6Am with translation efficiency and finely dissected the step-wised maternal RNA de-capping and de-tailing of different types of genes. Strikingly, we uncovered a subtle structural mechanism regulating poly(A) tails in oocytes: maternal RNA translation is temporarily suppressed by removing the poly(A) tails without complete degradation, while the poly(A)-tail regulators themselves depend strictly on translation initiated after meiotic resumption. Furthermore, we profiled single-cell RNA-multi-omic features of human oocytes with different qualities during in vitro culture maturation (IVM). Defects of epi-transcriptome features, including m6A, m6Am, m7G, and poly(A) structure of maternal RNA in the oocytes with poor quality, were detected. Conclusions Our results provided a valuable tool for RNAomics research and data resources provided novel insights into human oocyte maturation, which is helpful for IVM and oocyte selection for ART. |
| format | Article |
| id | doaj-art-e65c79b05c454d8d90388564f5e7d628 |
| institution | OA Journals |
| issn | 1741-7007 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj-art-e65c79b05c454d8d90388564f5e7d6282025-08-20T02:00:08ZengBMCBMC Biology1741-70072025-05-0123111810.1186/s12915-025-02250-7RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturationHuan Yao0Danru Zhang1Haixia Jin2Yanjie Guo3Yan Liu4Shengnan Wang5Tong Li6Shenli Yuan7Gang Lu8Yingpu Sun9Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for BioinformationCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityCUHK-SDU Joint Laboratory On Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong KongCUHK-SDU Joint Laboratory On Reproductive Genetics, School of Biomedical Sciences, The Chinese University of Hong KongCenter for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Omics technologies are widely applied in assisted reproductive technology (ART), such as embryo selection, investigation of infertility causes, and mechanisms underlying reproductive cell development. While RNAomics has shown great potential in investigating the physiology and pathology in female reproductive system, its applications are still not fully developed. More studies on epitranscriptomic regulation mechanisms and novel sequencing methods are needed to advance the field. Results Here, we developed a method named Cap to Tail sequencing application (C2T-APP) and simultaneously characterized the m7G cap, poly(A) tail structure, and gene expression level for the intact RNA molecules in single cells. C2T-APP distinguished the N6, 2′-O-dimethyladenosine modification (m6Am) from N 6-methyladenosine (m6A) modification with our published single-cell m6A sequencing (scm6A-seq) data. During oocyte maturation, we found a positive correlation of m7G and m6Am with translation efficiency and finely dissected the step-wised maternal RNA de-capping and de-tailing of different types of genes. Strikingly, we uncovered a subtle structural mechanism regulating poly(A) tails in oocytes: maternal RNA translation is temporarily suppressed by removing the poly(A) tails without complete degradation, while the poly(A)-tail regulators themselves depend strictly on translation initiated after meiotic resumption. Furthermore, we profiled single-cell RNA-multi-omic features of human oocytes with different qualities during in vitro culture maturation (IVM). Defects of epi-transcriptome features, including m6A, m6Am, m7G, and poly(A) structure of maternal RNA in the oocytes with poor quality, were detected. Conclusions Our results provided a valuable tool for RNAomics research and data resources provided novel insights into human oocyte maturation, which is helpful for IVM and oocyte selection for ART.https://doi.org/10.1186/s12915-025-02250-7RNA terminal structure detectionRNA modificationsRNA multi-omics in single cellsOocyte maturationMaternal RNA decay |
| spellingShingle | Huan Yao Danru Zhang Haixia Jin Yanjie Guo Yan Liu Shengnan Wang Tong Li Shenli Yuan Gang Lu Yingpu Sun RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation BMC Biology RNA terminal structure detection RNA modifications RNA multi-omics in single cells Oocyte maturation Maternal RNA decay |
| title | RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation |
| title_full | RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation |
| title_fullStr | RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation |
| title_full_unstemmed | RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation |
| title_short | RNA multi-omics in single cells reveal rhythmical RNA reshaping during human and mouse oocyte maturation |
| title_sort | rna multi omics in single cells reveal rhythmical rna reshaping during human and mouse oocyte maturation |
| topic | RNA terminal structure detection RNA modifications RNA multi-omics in single cells Oocyte maturation Maternal RNA decay |
| url | https://doi.org/10.1186/s12915-025-02250-7 |
| work_keys_str_mv | AT huanyao rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT danruzhang rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT haixiajin rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT yanjieguo rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT yanliu rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT shengnanwang rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT tongli rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT shenliyuan rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT ganglu rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration AT yingpusun rnamultiomicsinsinglecellsrevealrhythmicalrnareshapingduringhumanandmouseoocytematuration |