Page 23 - IBRO_RNA School_Abstract Book

Jain Niyati, Morgan C.E, Rife B.D, Salemi M, Tolbert B.S JBC 2015 291(5)
2331-44 Solution Structure of the HIV-1 Intron Splicing Silencer and its
Interactions with the UP1 Domain of hnRNP A1.
Niyati Jain, Hsuan-Chun Lin, Christopher E. Morgan, Michael Harris and Blanton
S. Tolbert PNAS 2017 Feb 28 ; 114(9) 2206-2211 “Rules of RNA specificity of

hnRNPA1 revealed by global and quantitative analysis of its affinity distribution”

Structural insights of RNA mediated gene regulation in
plants and higher eukaryotes
Mandar V. Deshmukh

CSIR-Centre for Cellular and Molecular Biology, Hyderabad,

India

The RNAi pathway initiation comprises the formation of a ternary complex

between Dicer, the initiator dsRNA and a modulator protein that binds to dsRNA (ds-
RBP). In response to evolutionary selection pressure and developmental require-
ments, higher eukaryotes have evolved an adaptable RNAi based gene regulation
pathway triggered by non-coding RNA. The ability of organisms to modify the key
components of the RNAi machinery is remarkable. The evolutionary divergence
in the RNAi pathway appears as custom-made alterations in Dicer and dsRBP
domain architecture and recruitment of uneven numbers of Dicers and dsRBP.
Why organisms modify key enzymes and proteins in the RNAi initiation despite
an identical outcome is still elusive. We hypothesize that the RNAi initiation is a
convoluted dynamic process tailored for evolutionary advantages to organisms.
To understand the origin and necessity of the evolutionary divergence in RNAi,
we have defined the functional roles of RDE-4 in C. elegans as well as DRB4

in A. thaliana in the last few years. We are currently exploring the structure-
function relationship in DRB2, DRB3, DRB5, and DRB7.2 in A. thaliana and
R2D2 in D. melanogaster using solution structure, biochemistry, and dynamics
studies. Subsequently, we anticipate assembling a ternary complex of Dier:ds-
RBP and corresponding initiator dsRNA for structural and mechanistic stud-
ies. So far, our results imply a fine balance in seemingly conserved and highly
homologous systems that are tuned to alter the fate of the small RNA mediated
gene silencing. Surprising heterogeneity in the structure and function of dsRBPs

suggests that the process of RNAi initiation is unique for each organism and is
dependent on the step-wise assembly of the Dicer, dsRBP, and the trigger small RNA.