Profile

Research

Publications

Team

Alumni

Rakesh S. Laishram, PhD

Scientist C and Wellcome Trust-India Alliance Intermediate Fellow

+91-471-2529592

laishram@rgcb.res.in

Rakesh_Laishram
Rakesh_Laishram

Rakesh S. Laishram, PhD

Scientist C and Wellcome Trust-India Alliance Intermediate Fellow

+91-471-2529592

laishram@rgcb.res.in

  • Profile

    • Ph.D. Molecular Biology/Biochemistry, Centre for DNA Fingerprinting and Diagnostics, Hyderabad – 2008
    • M.Sc. Biosciences, JamiaMilliaIslamia, New Delhi – 2003
    • B.Sc. Chemistry (Hons), Manipur University – 2001
    • July 2012 , Scientist C, Rajiv Gandhi Centre for Biotechnology, Trivandrum, India
    • March 2013 – August 2013, Visiting Associate Scientist, School of Medicine and Public Health, University of Wisconsin-Madison, USA
    • February 2008 – June 2012, Research Associate, University of Wisconsin-Madison, USA
    • Innovative Young Biotechnologist Award (IYBA), DBT India
    • Wellcome Trust, UK-DBT India Alliance Intermediate Fellowship – 2012
    • American Heart Association Scientist Development Award/Grant – 2012
    • DBT-Ramalingaswami Fellowship – 2012
    • American Heart Association Post-Doctoral Fellowship 2009-2010
    • CSIR Senior Research Fellowship 2005 -2008
    • CSIR Junior Research Fellowship 2003 -2005
    • JNCASR &IISc Summer Research Fellowship 2002
    • Gold Medal in Chemistry 2001, Manipur University
    • American Heart Association
    • “Faculty of 1000-Biology” – Associate faculty member
    • Indian National Science Congress Association
  • Research

    Post Transcriptional RNA processing in gene regulation

    The main focus of my laboratory is to understand the mechanism of post transcriptional gene regulation by RNA processing at the 3′-untranslated region (UTR), and how it affects various human diseases including cardiovascular diseases (CVDs) and cancer.

    Processing at the 3′-end of a precursor mRNA (pre-mRNA) is an essential step in eukaryotic gene expression. It is orchestrated by two tightly coupled processes – endonucleolytic cleavage followed by addition of a poly(A) tail (polyadenylation) at the 3′-UTR. The poly(A) tail of an mRNA is essential for its stability, translation, and export. Polyadenylation is carried out by enzymes called poly(A) polymerases (PAPs). Interestingly, more than 50% of genes in humans are alternatively polyadenylated at the 3′-UTR, to encode mRNA isoforms with different UTR lengths. The differential stability of mRNAs conferred by 3′-UTR isoforms modulate expression of genes involved in human diseases such as CVDs and cancer.

    Our lab aims to understand how regulation of mRNA 3′-end processing controls the expression of genes critical to several human diseases. We focus on the recently identified poly(A) polymerase, Star-PAP which selectively polyadenylates genes involved in oxidative stress response. The primary objective of our research is to understand the molecular mechanisms of Star-PAP and the canonical PAP. Also of interest ishow the alternative selection of multiple polyadenylation sites at the 3′-UTR is regulated tocontrol expression of specific genes. Further, we study the modulation of 3′-end RNA processing by multiple signalling pathways, nuclear phosphoinositides (PIP2), kinases and post translational modifications of PAPs.

  • Publications

    1. D. Ray, H. Kazan, K. Cook, M.Weirauch, H. N, X. Li, S. G, Albu, H. Zheng, H. Na, M. Irimia, L. Matzat, S. Smith, C. Y, S. K, B. Nabet, Rakesh S. Laishram, M. Qiao H. Lipshitz, F. Piano, A. Yang, A. corbett, R. Crastens, et. al. 2013. A compendium of RNA-binding motifs for decoding gene regulation. Nature. 499:172–177. (doi:10.1038/nature12311).
    2. Wiemin Li*, Rakesh S. Laishram*, and Richard A Anderson. 2013. The novel poly(A) polymerase Star-PAP is a signal-regulated switch at the 3′-end of mRNAs. Adv. Biol. Reg. 53: 64-76 (*First authorship)
    3. Weimin Li*, Rakesh S. Laishram*, ZheJi, Christy A. Barlow, Bin Tian, and Richard A. Anderson. 2012. Star-PAP Control of BIK Expression and Apoptosisis Regulated by Nuclear PIPKI and PKC Signaling. Mol. Cell. 45: 25-37. (*Equal First Authorship)
    4. Rakesh S. Laishram, Christy A. Barlow, and Richard A. Anderson. 2011. CKI isoforms α and ε regulates Star-PAP target messages by modulating Star-PAP polyadenylation activity. Nucleic Acid Research. 39 (18): 7961-7973.
    5. Rakesh S. Laishram and Richard A Anderson. 2010. The poly A polymerase Star-PAP controls 3’-end cleavage by promoting CPSF interaction with pre-mRNA. EMBO J. 29: 4132-4135. Highlighted by William F Marzluff. The EMBO Journal (2010) 29, 4066–4067.
    6. Christy A Barlow*, Rakesh S Laishram* and Richard A Anderson. 2010. Nuclear Phosphoinositide signaling- asignalling enigma wrapped in compartmental conundrum. Trends in Cell Biol. 20(1): 25-35. (*Equal first authorship and listed alphabetically)
  • Team


    Sudheesh A P, Ph.D. Student

    The work involves primarily elucidating the detail mechanistic pathway of 3'-end RNA processing mediated by the poly(A) polymerase Star-PAP, and delineate how it specifically affects human diseases such as cancer and CVDs. A major focus of the work involves examining various signalling pathways such as oxidative stress, DNA damage, and PI4,5P2 signalling in the nucleus, and how it regulates Star-PAP to control specific target mRNAs. This work will also include comparative proteomic and transcriptomic analysis of different poly(A) polymerases to define the target gene specificity, and phosphorylation patterns under different signalling conditions.

    Sudheesh-A-P
    Sudheesh-A-P

    Sudheesh A P, Ph.D. Student

    The work involves primarily elucidating the detail mechanistic pathway of 3'-end RNA processing mediated by the poly(A) polymerase Star-PAP, and delineate how it specifically affects human diseases such as cancer and CVDs. A major focus of the work involves examining various signalling pathways such as oxidative stress, DNA damage, and PI4,5P2 signalling in the nucleus, and how it regulates Star-PAP to control specific target mRNAs. This work will also include comparative proteomic and transcriptomic analysis of different poly(A) polymerases to define the target gene specificity, and phosphorylation patterns under different signalling conditions.

    Prajit J, Junior Research Fellow

    Comparative analysis of eukaryotic and prokaryotic polyadenylation:

    The role of poly (A) tails at the 3’-end of mRNAs is well studied in eukaryotes. The existence of poly (A) tail has also been reported in prokaryotic mRNAs, however the significance of such prokaryotic poly (A) tail on gene expression is not well established. While eukaryotic poly(A) tail stabilizes the mRNA, prokaryotic polyadenylation marks for degradation of RNA. The difference so far known of the two tails is that prokaryotes have shorter (A)-tail (mostly <50 adenosine nucleotides) compared to ~250 adenosine nucleotides of eukaryotic poly(A)-tails. In addition, eukaryotes contain distinct nuclear poly(A) binding protein which stabilizes the (A)-tail, while such notable proteins have not been identified in prokaryotes. We investigate the difference between the two poly(A) tails (bacterial and eukaryotic) which causes a contrasting function. We also compare E. coli poly(A) polymerase with eukaryotic counterparts such as Star-PAP and PAPα – their properties, activity, kinetics and cellular function.

    Prajit-j
    Prajit-j

    Prajit J, Junior Research Fellow

    Comparative analysis of eukaryotic and prokaryotic polyadenylation:

    The role of poly (A) tails at the 3’-end of mRNAs is well studied in eukaryotes. The existence of poly (A) tail has also been reported in prokaryotic mRNAs, however the significance of such prokaryotic poly (A) tail on gene expression is not well established. While eukaryotic poly(A) tail stabilizes the mRNA, prokaryotic polyadenylation marks for degradation of RNA. The difference so far known of the two tails is that prokaryotes have shorter (A)-tail (mostly <50 adenosine nucleotides) compared to ~250 adenosine nucleotides of eukaryotic poly(A)-tails. In addition, eukaryotes contain distinct nuclear poly(A) binding protein which stabilizes the (A)-tail, while such notable proteins have not been identified in prokaryotes. We investigate the difference between the two poly(A) tails (bacterial and eukaryotic) which causes a contrasting function. We also compare E. coli poly(A) polymerase with eukaryotic counterparts such as Star-PAP and PAPα – their properties, activity, kinetics and cellular function.

    Nimmy Mohan, Junior Research Fellow

    Role of RNA binding motif 10 (RBM10) in gene expression and alternative polyadenylation

    RBM10 is a nuclear protein that contains an RNA recognition motif, the exact function of which is not clear yet. However, it has been implicated in alternative splicing, X-linked disorder-TARP syndrome, and apoptosis. We observed that RBM10 associates with Star-PAP, but earlier studies on factors associated with canonical PAP failed to detect RBM10 in the PAPα complex. We explore the role of RBM10 in the Star-PAP mediated 3’-end processing and alternative polyadenylation, and (if any) on the specificity for Star-PAP target genes (stress response and antitumor). We will also investigate role of RBM10 in gene regulation and define its genome wide target genes.

    Nimmy-_Mohan
    Nimmy-_Mohan

    Nimmy Mohan, Junior Research Fellow

    Role of RNA binding motif 10 (RBM10) in gene expression and alternative polyadenylation

    RBM10 is a nuclear protein that contains an RNA recognition motif, the exact function of which is not clear yet. However, it has been implicated in alternative splicing, X-linked disorder-TARP syndrome, and apoptosis. We observed that RBM10 associates with Star-PAP, but earlier studies on factors associated with canonical PAP failed to detect RBM10 in the PAPα complex. We explore the role of RBM10 in the Star-PAP mediated 3’-end processing and alternative polyadenylation, and (if any) on the specificity for Star-PAP target genes (stress response and antitumor). We will also investigate role of RBM10 in gene regulation and define its genome wide target genes.

    Divya Theja Kandala, Project Assistant

    To elucidate the mechanism of specificity of different poly (A) polymerases (PAPs )to regulate distinct poly(A) site(s)

    We focus on two functionally similar but distinct nuclear PAPs, Star-PAP and PAPα. Although the two PAPs share common 3'-end processing factors, they exist in distinct complexes and regulate specific target mRNAs. We aim to identify the components of each PAP complex using mass spectrometry analysis. The associated factors will be compared, and the roles of unique proteins (if any) associated in the specificity and poly (A) site selection of respective target UTRs will be defined. Earlier reports suggest that certain 3'-end processing factors such as CstF or CF Im may be dispensable for Star-PAP-mediated polyadenylation unlike the canonical PAP. The significance of such factors in the 3'-end processing mediated by each PAP will be investigated. In addition, the competitive association of Star-PAP and PAPα on each target genes will be studied by Chip, and/or ChIP on ChiP experiments. We also explore the competition of PAPs for common RNA processing factors such as CPSF to regulate alternative poly(A) site selection.

    Divya_Kandal
    Divya_Kandal

    Divya Theja Kandala, Project Assistant

    To elucidate the mechanism of specificity of different poly (A) polymerases (PAPs )to regulate distinct poly(A) site(s)

    We focus on two functionally similar but distinct nuclear PAPs, Star-PAP and PAPα. Although the two PAPs share common 3'-end processing factors, they exist in distinct complexes and regulate specific target mRNAs. We aim to identify the components of each PAP complex using mass spectrometry analysis. The associated factors will be compared, and the roles of unique proteins (if any) associated in the specificity and poly (A) site selection of respective target UTRs will be defined. Earlier reports suggest that certain 3'-end processing factors such as CstF or CF Im may be dispensable for Star-PAP-mediated polyadenylation unlike the canonical PAP. The significance of such factors in the 3'-end processing mediated by each PAP will be investigated. In addition, the competitive association of Star-PAP and PAPα on each target genes will be studied by Chip, and/or ChIP on ChiP experiments. We also explore the competition of PAPs for common RNA processing factors such as CPSF to regulate alternative poly(A) site selection.

  • Alumni