Functional association analysis

on protein sumoylation and RNA binding

Xiaotong Yao

Mentors: Rebecca Bish, Christine Vogel

16^th Jan 2014

Outline

• Introduction
• Progress
• Discussion

Introduction--SUMO

• Small Ubiquitin-like MOdifier

a post-translational modification

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• signature C-terminal GG

targeting lysine

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• involved in various biological processes

e.g. protein stability, nuclear-cytoplasm

transport, transcriptional regulation

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Flotho, A., & Melchior, F. (2013). Sumoylation: A Regulatory Protein Modification in Health and Disease. Annual review of biochemistry, 82(1).

Introduction

Our hypothesis is

RNA binding proteins tend to be sumoylated more often than average

• Becky’s inspiration from RBP research
• essential for yeast & human cells
• no former integrative research

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We plan to answer this question

• statistically: enough evidence?
• evolutionarily: human & yeast?

Progress--get data

list of sumo targets in yeast

Progress--get data

list of RNA binding proteins in yeast from Gene Ontology

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or from Superfamily

which turned out not a very good choice...

Progress--hypergeometric test

From an urn(total proteome) consisting of

m white balls(RNA binding proteins) and n black balls(complementary set of RBP),

randomly drawn k(number of proteins in your interest list, here SUMO targets) balls,

and q(the quantity of intersection of SUMO targets and RBPs)

out of these k balls are white(RNA binding protein).

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H0: No association between RNA binding and sumoylation, any concurrence is purely random effect, and the number of concurrence conforms to hypergeometric distribution with these parameters(m, n, k, q).

HA: There is a higher probability of concurrence of RNA binding and sumoylation.

Progress--Results

• non-redundant lists of sumo targets: 555 in yeast, 1861 in human
• RNA binding protein list from Gene Ontology: 561 in yeast, 969 in human
• choose sizes of proteomes: 5820 in yeast, 20597 in human
• hypergeometric probabilities: <10^-6 in yeast, <10^-80 in human

Discussion

Current result indicates

• significant enrichment of RNA binding in sumo target list, in both organisms

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Potential misleading factors in current result

• heterogenous sumo target data
• incomplete sumo data

Discussion--misleading factors

Discussion

Current result indicates

• significant enrichment of RNA binding in sumo target list, in both organisms

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Potential misleading factors in current result

• heterogenous sumo target data
• incomplete sumo data

Further job

• any other function shows enrichment in sumo targets
• if sumo target consensus motif show up in RBPs
• hypothesize why it is so