MicroRNAs (miRNAs) belong to a class of small non-coding RNAs (ribonucleic acids), approximately 22 nucleotides,  that often silence the expression of protein-coding genes by binding to their cognate messenger RNAs (mRNAs). Significant advances have been made in the discovery of miRNAs and their respective target genes during a number of physiological processes such as cellular development and differentiation. Deregulation of miRNA function is closely associated with several immune cell diseases, particularly cancer.

A team led by Prof. Jagan Pongubala at the Department of Animal Biology, School of Life Sciences, University of Hyderabad (UoH) has probed the genome-wide expression accompanied by functional analysis of miRNAs during lymphoid (B and T) lineage commitment. This study (Nikhat et. al., 2021) demonstrates that miRNAs act in a combinatorial and cell type-specific manner to reinforce B and T lineage-specific gene expression programs by repressing inappropriate genes. The absence of these miRNAs in developing lymphocytes results in a mixed-lineage gene expression pattern. Interestingly, most of these miRNAs turned out to be regulated by primary lineage-specific transcription factors, highlighting the complexity of regulatory mechanisms orchestrating B and T lymphocyte differentiation. Such context-dependent, genome-wide analyses of miRNAs combined with functional studies represent one of the first comprehensive investigations to understand the role of miRNAs in developing lymphocytes. Collectively, these studies present a general paradigm for the role of miRNAs in regulating cell-fate decisions in other hematopoietic lineages and for understanding the molecular basis of diseases caused by dysregulation of miRNAs during lymphoid malignancies.

Prof. B. J. Rao, the Vice-Chancellor of University of Hyderabad, congratulated Prof. Jagan Pongubala and his team for their excellent work and anticipated more such high-impact publications from the University would foster an environment that sustains highest standards of scholarship and learning.

The research team included Sameena Nikhat, Anurupa D. Yadavalli, Arpita Prusty, Priyanka K. Narayan, Dasaradhi Palakodeti, Cornelis Murre, and Jagan M. R. Pongubala (2021). A regulatory network of microRNAs confers lineage commitment during early developmental trajectories of B and T lymphocytes. PNAS November 16, 2021118 (46) e2104297118; https://doi.org/10.1073/pnas.2104297118

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