Comprehensive mapping of alternative polyadenylation site usage and its dynamics at single-cell resolution

Wang Junliang1,2; Chen Wei3; Yue Wenjun2; Hou Wenhong2; Rao Feng2; Zhong Hanbing2; Qi Yuanming1; Hong Ni2; Ni Ting3; Jin Wenfei2

2022-12-01

10.1073/pnas.2113504119

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   影响因子和分区

0027-8424

1091-6490

Alternative polyadenylation (APA) plays an important role in posttranscriptional gene regulation such as transcript stability and translation efficiency. However, our knowledge about APA dynamics at the single-cell level is largely unexplored. Here, we developed single-cell polyadenylation sequencing, a strand-specific approach for sequencing the 3' end of transcripts, to investigate the landscape of APA at the single-cell level. By analyzing several cell lines, we found many genes using multiple polyA sites in bulk data are prone to use only one polyA site in each single cell. Interestingly, cell cycle genes were significantly enriched in genes with high variation in polyA site usages. Furthermore, the 414 genes showing a polyA site usage switch after cell synchronization enriched cell cycle genes, while the differentially expressed genes after cell synchronization did not enrich cell cycle genes. We further identified 812 genes showing polyA site usage changes between neighboring cell cycles, which were grouped into six clusters, with cell phase-specific functional categories enriched in each cluster. Deletion of one polyA site in MSL1 and SCCPDH results in slower and faster cell cycle progression, respectively, supporting polyA site usage switch played an important role in cell cycle. These results indicate that APA is an important layer for cell cycle regulation.

single-cell RNA-sequencing single-cell polyadenylation sequencing alternative polyadenylation cell cycle cell cycle synchronization

SCI

英语

NI论文

通讯

National Key Research and Development Program of China["2021YFA0909300","2021YFF1200900"] ; National Natural Science Foundation of China[32170646] ; Shenzhen Science and Technology Program[KQTD20180411143432337] ; Shenzhen Innovation Committee of Science and Technology["JCYJ20180504170158430","JCYJ20220818100401003","ZDSYS20200811144002008"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000972701200001

NATL ACAD SCIENCES

BIOLOGY & BIOCHEMISTRY;CLINICAL MEDICINE;MULTIDISCIPLINARY;PLANT & ANIMAL SCIENCE;ENVIRONMENT/ECOLOGY;SOCIAL SCIENCES, GENERAL;MICROBIOLOGY;ECONOMICS BUSINESS;IMMUNOLOGY;MATERIALS SCIENCE;MATHEMATICS;SPACE SCIENCE;MOLECULAR BIOLOGY & GENETICS;PHARMACOLOGY & TOXICOLOGY;CHEMISTRY;PSYCHIATRY/PSYCHOLOGY;NEUROSCIENCE & BEHAVIOR;PHYSICS;GEOSCIENCES;AGRICULTURAL SCIENCES;ENGINEERING

Web of Science

1.School of Life Sciences, Zhengzhou University
2.Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology,
3.State Key Laboratory of Genetic Engineering & Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Shanghai Cancer Center, Fudan University,

Wang Junliang,Chen Wei,Yue Wenjun,et al. Comprehensive mapping of alternative polyadenylation site usage and its dynamics at single-cell resolution[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2022,119(49).

Wang Junliang.,Chen Wei.,Yue Wenjun.,Hou Wenhong.,Rao Feng.,...&Jin Wenfei.(2022).Comprehensive mapping of alternative polyadenylation site usage and its dynamics at single-cell resolution.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119(49).

Wang Junliang,et al."Comprehensive mapping of alternative polyadenylation site usage and its dynamics at single-cell resolution".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119.49(2022).