Lab in the News
The Wistar Institute Appoints Bin Tian, Ph.D., as Professor in the Cancer Center and Co-director of the Center for Systems & Computational Biology
PHILADELPHIA — (May, 1, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, announces the appointment of molecular systems biologist Bin Tian, Ph.D., as professor in the Cancer Center.
The Tian Laboratory
Expression of the genetic code, from DNA to protein, can be regulated at different stages, much of which takes place after RNA is made. The Tian lab studies RNA biology using a variety of approaches including computational biology, molecular biology, and genomics. They have contributed important knowledge on the mechanisms and consequences of alternative polyadenylation (APA) in development and disease.
Yange Cui, Ph.D.
Chuwei Zhong, Ph.D.
Multiple graduate student and postdoctoral positions are available in the Tian lab. Motivated candidates interested in experimental studies, or computational research or both are encouraged to inquire about the positions by contacting Dr. Bin Tian, firstname.lastname@example.org.
GENETICS AND GENOMICS OF 3’ END PROCESSING
In eukaryotes, almost all protein-coding mRNAs and long non-coding RNAs (lncRNAs) transcribed by RNA polymerase II employ cleavage and polyadenylation (CPA) for 3' end processing. CPA is also coupled with termination of transcription. A gene can have multiple cleavage and polyadenylation sites (PASs), resulting in mRNA isoforms with different coding sequences and/or 3' untranslated regions (3'UTRs), a phenomenon called alternative cleavage and polyadenylation (APA). Using bioinformatics and genomics, the Tian lab was among the first to report the widespread nature of APA in human and mouse genes. Through deep sequencing efforts from many labs in the last few years, it is now clear that APA is widespread throughout all eukaryotes and a PAS can vary substantially in surrounding motifs. The Tian lab is now studying how PASs evolve across species, and how they impact evolution of different types of genes, including promoter-associated upstream antisense RNAs (uaRNAs), enhancer-associated RNAs (eRNAs), RNAs expressed from transposable elements, etc.
MOLECULAR MECHANISMS OF ALTERNATIVE POLYADENYLATION
APA of a gene can change in different conditions. The Tian lab was the first to report global biases in APA site usage across human tissues and in cell differentiation. They also revealed widespread intronic polyadenylation (IPA) and the relevance of 5' splice site strength and intron size to IPA. Over the last few years, the lab has elucidated mechanisms of PAS usage control at different levels, including regulation by core cleavage and polyadenylation factors, splicing factors, promoter activity, transcriptional elongation rate, nuclear export factors, etc. They have worked with several biological conditions where global APA changes are conspicuous, including differentiation of muscle and fat cells, cardiac hypertrophy, spermatogenesis, UV damage, long-term potentiation of neurons, neurogenesis, cellular stress, and secretory cell formation. They are currently studying molecular underpinnings of APA regulation in several differentiation lineages, under stress conditions, and during secretory cell formation.
FUNCTIONS OF 3' UTRS IN CELL DIFFERENTIATION AND STRESS
The 3'UTR plays regulatory roles in mRNA metabolism, including mRNA decay, translation, and localization. Sequence and structural motifs embedded in 3'UTRs contribute to 3'UTR functions through interaction with their cognate RNA binding proteins (RBPs), microRNAs (miRNAs), or lncRNAs. The Tian lab has used systems biology approaches to study these regulatory mechanisms. They have uncovered sequence motifs for mRNA stability in myoblast cells, pluripotent stem cells, differentiating neurons, and stressed cells; they examined RNA structures in 3'UTRs; they studied various RBPs, such as UPF1, Staufen 1, TIA1, etc. They are currently studying how 3'UTRs are involved in mRNA decay, translational control, and subcellular localization in different cell types and conditions, such as differentiating neurons, stressed cells, and secretory cells.
Databases and Software
PolyA_DB is a web-based database created by the Tian lab for comprehensive cataloging of pre-mRNA cleavage and polyadenylation (polyA) sites in multiple species.
Zheng, D., Cho, H., Wang, W., Rambout, X., Tian, B., Maquat, L. "3'READS + RIP Defines Differential Staufen1 Binding to Alternative 3'UTR Isoforms and Reveals Structures and Sequence Motifs Influencing binding and Polysome Association." RNA. 2020 Nov;26(11):1621-1636. doi: 10.1261/rna.076133.120. Epub 2020 Aug 12.
Cheng, L.C., Zheng, D., Baljinnyam, E., Sun, F., Ogami, K., Yeung, P.L., Hoque, M., Lu, C., Manley, J.L., Tian, B. "Widespread Transcript Shortening Through Alternative Polyadenylation in Secretory Cell Differentiation." Nat Commun. 2020 Jun 23;11(1):3182. doi: 10.1038/s41467-020-16959-2.
Wang, R., Tian, B. “APAlyzer: a bioinformatic package for analysis of alternative polyadenylation isoforms.” Bioinformatics. 2020 Apr 22; pii: btaa266. doi: 10.1093/bioinformatics/btaa266. Epub ahead of print
Wang, R., Zheng, D., Wei, L., Ding, Q., Tian, B. “Regulation of intronic polyadenylation by PCF11 impacts mRNA expression of long genes." Cell Rep. 2019, Mar 5;26(10):2766-2778. doi: 10.1016/j.celrep.2019.02.049.
Chen, S., Wang, R., Zheng, D., Zhang, H., Chang, X., Wang, K., Li, W., Fan, J., Tian, B., Cheng, H. “The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export.” Mol Cell. 2019 April 4;74:118-131. Doi:10.1016/j.molcel.2019.01.026
Italo Tempera, Ph.D.
Associate Professor, Gene Expression & Regulation Program, The Wistar Institute Cancer Center