한빛사 논문
Seungjae Lee1, Yen-Chung Chen2, FCA Consortium*, Austin E. Gillen3,4,5, J. Matthew Taliaferro5,6, Bart Deplancke7, Hongjie Li8,9 & Eric C. Lai1#
1Developmental Biology Program, Sloan Kettering Institute, 1275 York AveBox 252 New York, NY 10065, USA. 2Department of Biology, New York University, New York, NY 10013, USA. 3Division of Hematology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 4Rocky Mountain Regional VA Medical Center, Aurora, CO, USA. 5RNA Bioscience Initiative, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 6Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 7Laboratory of Systems Biology and Genetics, Institute of Bio-engineering & Global Health Institute, School of Life Sciences, EPFL, CH-1015 Lausanne, Switzerland. 8Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA. 9Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. *A list of authors and their affiliations appears at the end of the paper.
#Corresponding author.
Abstract
Most genes in higher eukaryotes express isoforms with distinct 3’ untranslated regions (3’ UTRs), generated by alternative polyadenylation (APA). Since 3’ UTRs are predominant locations of post-transcriptional regulation, APA can render such programs conditional, and can also alter protein sequences via alternative last exon (ALE) isoforms. We previously used 3’-sequencing from diverse Drosophila samples to define multiple tissue-specific APA landscapes. Here, we exploit comprehensive single nucleus RNA-sequencing data (Fly Cell Atlas) to elucidate cell-type expression of 3’ UTRs across >250 adult Drosophila cell types. We reveal the cellular bases of multiple tissue-specific APA/ALE programs, such as 3’ UTR lengthening in differentiated neurons and 3’ UTR shortening in spermatocytes and spermatids. We trace dynamic 3’ UTR patterns across cell lineages, including in the male germline, and discover new APA patterns in the intestinal stem cell lineage. Finally, we correlate expression of RNA binding proteins (RBPs), miRNAs and global levels of cleavage and polyadenylation (CPA) factors in several cell types that exhibit characteristic APA landscapes, yielding candidate regulators of transcriptome complexity. These analyses provide a comprehensive foundation for future investigations of mechanisms and biological impacts of alternative 3’ isoforms across the major cell types of this widely-studied model organism.
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