Structural delineation of stem-loop RNA binding by human TAF15 protein

Kashyap Maruthi, Akshay Kumar Ganguly, Neel Sarovar Bhavesh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Human TATA binding protein associated factor 2 N (TAF15) and Fused in sarcoma (FUS) are nucleic acid binding proteins belonging to the conserved FET family of proteins. They are involved in diverse processes such as pre-mRNA splicing, mRNA transport, and DNA binding. The absence of information regarding the structural mechanism employed by the FET family in recognizing and discriminating their cognate and non-cognate RNA targets has hampered the attainment of consensus on modes of protein-RNA binding for this family. Our study provides a molecular basis of this RNA recognition using a combination of solution-state NMR spectroscopy, calorimetry, docking and molecular dynamics simulation. Analysis of TAF15-RRM solution structure and its binding with stem-loop RNA has yielded conclusive evidence of a non-canonical mode of RNA recognition. Rather than classical stacking interactions that occur across nitrogen bases and aromatic amino acids on ribonucleoprotein sites, moderate-affinity hydrogen bonding network between the nitrogen bases in the stem-loop RNA and a concave face on the RRM surface primarily mediate TAF15-RRM RNA interaction. We have compared the binding affinities across a set of single-stranded RNA oligonucleotides to conclusively establish that RNA binding is dependent upon structural elements in the RNA rather than sequence.

Original languageEnglish (US)
Article number17298
JournalScientific Reports
Volume5
DOIs
StatePublished - Nov 27 2015
Externally publishedYes

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RNA
TATA-Binding Protein Associated Factors
Nitrogen
Aromatic Amino Acids
Calorimetry
Ribonucleoproteins
RNA-Binding Proteins
human TAF15 protein
RNA Precursors
Molecular Dynamics Simulation
Hydrogen Bonding
Oligonucleotides
Sarcoma
Nucleic Acids
Carrier Proteins
Magnetic Resonance Spectroscopy
Messenger RNA
DNA
Proteins

ASJC Scopus subject areas

  • General

Cite this

Structural delineation of stem-loop RNA binding by human TAF15 protein. / Maruthi, Kashyap; Ganguly, Akshay Kumar; Bhavesh, Neel Sarovar.

In: Scientific Reports, Vol. 5, 17298, 27.11.2015.

Research output: Contribution to journalArticle

Maruthi, Kashyap ; Ganguly, Akshay Kumar ; Bhavesh, Neel Sarovar. / Structural delineation of stem-loop RNA binding by human TAF15 protein. In: Scientific Reports. 2015 ; Vol. 5.
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