Genetic architecture of RBP-coding genes

Abstract
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[*]fandrade@ime.usp.br RNA-binding proteins (RBP) is an important class of proteins that have a major role in post-transcription genetic regulation (PTGR), a process which regulates the production of proteins and also many modifications in the mature RNA molecules. Linear Mixture Models and Bayesian Models are currently being applied to study the genetic architecture of RBP-coding genes.

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[*]fandrade@ime.usp.br

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[*]fandrade@ime.usp.br

Introduction

Gene expression has been studied in an extensive way, but it has focused on quantification of mRNA. With this knowledge of gene expression, recently there has been many attempts to explain different complex characters, specially diseases, with changes in mRNA levels. The major problem with this idea is that the mRNA molecules, per se, do not have any direct role in cell function other than carrying information from DNA to be translated in ribosomes. Enzymatic, structural and regulatory roles are played by proteins and other non-coding RNA. Also, the correlation between what is being measured (mRNA) and what actually might influence phenotypes (proteins) is low (Wu 2013, Hause 2014, Schwanhäusser 2011).

We can understand the relationship between levels of mRNA and proteins better when we consider the Post Transcription Genetic Regulation (PTGR). PTGR involves, among others, determining mRNA half-lives and the rate these molecules are translated into proteins. Considering processes from PTGR increases substantially the correlations between mRNA and protein quantification (Schwanhäusser 2011). This result, indicates that, when we try to relate gene expression to complex phenotypes, we must consider PTGR.

Of the many molecules that may have a part in PTGR, RNA-binding proteins (RBP) is a important group of proteins. These proteins are characterized by domains that specifically targets RNA (Hasan 2014, Gerstberger 2014, Castello 2012) and are involved in many processes with mRNA, including mRNA stability (Hasan 2014).

As the scenario described above suggests, RBP may help relating mRNA and protein levels. So, understanding the regulatory architecture of RBP-coding genes, and identifying possible mRNA targeted by RBP is crucial to a better understanding of PTGR.

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[*]fandrade@ime.usp.br

Objective

The main objective is to understand the regulatory architecture of RBP, both in mRNA and protein level.

This objective can be split into three specific objectives:

  1. 1.

    estimate the narrow sense heritability (\(h^{2}\)) of RBP-coding genes mRNA and their respective proteins;

  2. 2.

    identify markers associated with the phenotypes (RBP-coding genes mRNA and their respective proteins);

  3. 3.

    identify markers that interact between mRNA and proteins, in order to estimate a network of RBP interactions.