Projects

I am obsessed with various state-of-the-art high-throughput transcriptome profiling techniques, and devote myself to integrate different computational analysis methods with molecular biology experiments to solve some important and interesting biological questions concerning the complexity of human gene regulation network.

Circular RNAs

Circular RNAs, as a newly emerging RNA species, have been identified in multiple species and different cell lines. But knowledge of their biogenesis machinery has remained limited. My work revealed some novel biogenesis clues for two distinct types of circular RNAs. One type of circular RNAs is derived from excised introns (circular intronic RNAs), and we discovered their processing depends on a consensus motif containing a 7 nt GU-rich element near the 5’ splice site and an 11 nt C-rich element close to the branchpoint site (Mol Cell, 2013). Another type of circular RNAs is from back-spliced exons (exonic circular RNAs), and we demonstrated that exon circularization is dependent on flanking intronic complementary sequences (e.g. IRAlus) and the efficiency of exon circularization can be regulated by competition between RNA pairing across flanking introns or within individual introns (Cell, 2014).

  • Zhang Y*, Zhang XO*, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L†, Chen LL†. Circular intronic long noncoding RNAs. Mol Cell. 2013, 51:792-806. Paper GitHub
  • Zhang XO*, Wang HB*, Zhang Y, Lu X, Chen LL†, Yang L†. Complementary sequence-mediated exon circularization. Cell. 2014, 159:134-147. Paper GitHub
  • Zhang XO*, Dong R*, Zhang Y*, Zhang JL, Luo Z, Zhang J, Chen LL†, Yang L†. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res, 2016, 26:1277-1287. Paper GitHub
  • Dong R, Zhang XO, Zhang Y, Ma XK, Chen LL, Yang L†. CircRNA-derived pseudogenes. Cell Res. 2016, 26:747-750. Paper GitHub

Alternative Splicing

Alternative splicing allows exons to be joined in different variations to form alternative transcripts, which greatly increases the diversity of transcriptome encoded by a limited number of genes. My projects mainly focused on how alternative splicing contribute to the regulation of long noncoding RNAs (lncRNAs). By exploring non-polyadenylated transcriptomes, one new type of lncRNAs with snoRNA on their ends (snoRNA-related lncRNAs, sno-lncRNAs) were identified from multiple species, and we revealed that the expression of sno-lncRNAs is species-specific and that their processing is closely linked to alternative splicing of their parent genes (BMC Genomics, 2014). Alternative splicing analysis of non-polyadenylated transcriptomes also helps us to systematically annotated different types of alternative back-splicing and alternative splicing events in circRNAs from various cell lines, and compared with their linear cognate RNAs, circRNAs exhibited distinct patterns of alternative back-splicing and alternative splicing (Genome Res, 2016).

  • Zhang XO*, Yin QF*, Wang HB, Zhang Y, Chen T, Zheng P, Lu X, Chen LL†, Yang L†. Species-specific alternative splicing leads to unique expression of sno-lncRNAs. BMC Genomics. 2014, 15:287. Paper
  • Zhang XO, Yin QF, Chen LL, Yang L†. Gene expression profiling of non-polyadenylated RNA-seq across species. Genomics Data. 2014, 2:237-241. Paper
  • Zhang XO*, Dong R*, Zhang Y*, Zhang JL, Luo Z, Zhang J, Chen LL†, Yang L†. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res, 2016, 26:1277-1287. Paper GitHub

Others

I also enjoy involving in the open source community and
contributing to push forward the application of open source softwares
in computational biology.