Research in Bin Tian Laboratory Lab Home

Our lab is interested in RNA biology, especially regulation of mRNA processing and metabolism in development and disease. We employ a variety of interdisciplinary approaches in our studies, including bioinformatics, genomics, genetics, molecular biology, and cell biology.
Major research areas:

Genetics and genomics of cleavage and polyadenylation sites.

In eukaryotes, almost all protein-coding mRNAs and long non-coding RNAs (lncRNAs) transcribed by RNA polymerase II (RNP II) employ cleavage and polyadenylation (CPA) for 3' end processing. CPA is also coupled with termination of transcription. A gene can have multiple sites for CPA (or PASs), resulting in mRNA isoforms with different coding sequences (CDSs) and/or 3' untranslated regions (3'UTRs), a phenomenon called alternative cleavage and polyadenylation (APA). Using bioinformatics, our lab was among the first to report the widespread nature of APA in human and mouse genes. We also systematically defined key motifs surrounding a PAS. It is now clear, through deep sequencing efforts from many labs, that APA is widespread throughout all eukaryotes and a PAS can vary substantially in surrounding motifs. We are now trying to address how PASs are conserved and vary across species, and how they contribute to evolution of transcriptional units of different kinds, including promoter-associated upstream antisense RNAs (uaRNAs), enhancer-associated RNAs (eRNAs), RNAs expressed from transposable elements, etc. We are also interested in how PAS variation in the human population contributes to clinical conditions.

Representative publications:

  • Tian B, Hu J, Zhang H, Lutz CS. (2005). A large-scale analysis of mRNA polyadenylation of human and mouse genes. Nucleic Acids Res. 33:201-212.
  • Hu J, Lutz CS, Wilusz J, Tian B. (2005). Bioinformatic identification of candidate cis-regulatory elements involved in human mRNA polyadenylation. RNA 11:1485-93.
  • Hoque M*, Ji Z*, Zheng D, Luo W, Li W, You B, Park JY, Yehia G, Tian B. (2013). Analysis of alternative cleavage and polyadenylation by 3'region extraction and deep sequencing. Nat Methods. 10:133-9.
  • Liu X, Hoque M, Larochelle M, Lemay JF, Yurko N, Manley JL, Bachand F, Tian B. (2017). Comparative Analysis of Alternative Polyadenylation in S. cerevisiae and S. pombe. Genome Res. 27:1685-1695.
  • Wang R, Zheng D, Yehia G, Tian B. (2018). A compendium of conserved cleavage and polyadenylation events in mammals. Genome Res. 28:1427-1441.

  • Molecular mechanisms of APA.

    APA of a gene can change in different conditions. Our lab was among the first to report global biases in APA site usage across human tissues, and in cell differentiation. We also revealed widespread intronic polyadenylation (IPA) and the relevance of 5' splice site and intron size to IPA. Over the last few years, we have been elucidating mechanisms of PAS usage control at different levels, including regulation by core cleavage and polyadenylation factors, splicing factors, promoter activity, transcriptional elongation rate, and nuclear export factors. We 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, and cellular stress.

    Representative publications:

  • Zhang H, Lee JY, Tian B. (2005). Biased alternative polyadenylation in human tissues. Genome Biol. 6:R100.
  • Tian B, Pan Z, Lee JY. (2007). Widespread mRNA polyadenylation events in introns indicate dynamic interplay between polyadenylation and splicing. Genome Res. 17:156-65.
  • Ji Z*, Lee JY*, Pan Z*, Jiang B, Tian B. (2009). Progressive lengthening of 3'untranslated regions of mRNAs by alternative polyadenylation during mouse embryonic development. Proc Natl Acad Sci USA. 106:7028-33.
  • Li W, You B, Hoque M, Luo W, Park JY, Ji Z, Zheng D, Gunderson SI, Kalsotra A, Manley JL, Tian B. (2015). Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation. PLoS Genet. 11:e1005166.
  • Chen S*, Wang R*, Zheng D*, Zhang H*, Chang X, Wang K, Li W, Fan J, Tian B#, Cheng H#. (2019) The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export. Mol Cell, Mol Cell. 1(74):118-131.

  • Functions of 3'UTR 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 by interacting with their cognate RNA binding proteins (RBPs), microRNAs (miRNAs), or lncRNAs. Our lab has used systems approaches to study these regulatory mechanisms. We uncovered sequence motifs for mRNA stability in myoblast cells, pluripotent stem cells, differentiating neurons, and stressed cells; we examined RNA structures in 3'UTRs; we studied various RBPs, such as UPF1, Staufen 1, TIA1, etc. We are currently studying how 3'UTRs are involved in mRNA decay, translational control, and localization in cell differentiation and stress, especially in the neuronal setting.

    Representative publications:

  • Neff AT, Lee JY, Wilusz J, Tian B, Wilusz CJ. (2012). Global analysis reveals multiple pathways for unique regulation of mRNA decay in induced pluripotent stem cells. Genome Res. 22:1457-67.
  • Kurosaki T, Li W, Hoque M, Popp MWL, Ermolenko D, Tian B, Maquat LE. (2014). A post-translational regulatory switch on UPF1 controls targeted mRNA degradation. Genes Dev. 28:1900-16.
  • Dai W, Li W, Hoque M, Li Z, Tian B#, EMakeyev EV#. (2015). A post-transcriptional mechanism pacing expression of neural genes with precursor cell differentiation status. Nat Commun. 6:7576.
  • Elbarbary RA, Miyoshi K, Myers JR, Du P, Ashton JM, Tian B, Maquat LE. (2017). Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition. Science. 356:859-862.
  • Zheng D*, Wang R*, Ding Q, Wang T, Xie B, Wei L, Zhong Z, Tian B. (2018). Cellular stress alters 3'UTR landscape through alternative polyadenylation and isoform-specific degradation. Nat Commun. 9:2268.

    Last updated: 2/22/2019
    Tian Lab @ Rutgers University - New Jersey Medical School