Systematic characterization of unconventional RNA binding proteins

 描述（由申请人提供）：拟议研究的目标是系统地调查新描述的“非常规RNA结合蛋白”（ucRBP）的分子功能。ucRBP结合细胞中的RNA，但尚未与序列特异性RNA结合相关。因此，它们可能代表了迄今为止未知的RNA调节子的大库：迄今为止已经鉴定了约800种ucRBP。我们提出的分析将（i）确定每种ucRBP是否结合特异性RNA序列或特异性RNA转录物;（ii）鉴定ucRBP的蛋白质伴侣，其可以赋予特异性和/或可以作为效应物;（iii）应用先进的计算分析，从大规模数据集和文献中查明ucRBP的生物化学和生理功能，及（iv）将更详细地探讨ucRBP的选定子集的功能。总之，这些快速和具有成本效益的分析将阐明和验证ucRBP的功能，为绘制新的调控机制铺平道路，确定许多人类序列变体的潜在功能，并将对从基因调控到人类遗传学的领域产生广泛影响。

 DESCRIPTION (provided by applicant): The goal of the proposed study is to systematically survey the molecular functions of newly-described "unconventional RNA-binding proteins" (ucRBPs). ucRBPs bind RNA in cells, but have not yet been associated with sequence-specific RNA binding. Therefore, they potentially represent a large pool of heretofore-unknown RNA regulators: ~800 ucRBPs have been identified to date. The analyses we propose will (i) determine whether each ucRBP binds specific RNA sequences or specific RNA transcripts; (ii) identify protein partners of the ucRBPs, which may confer specificity, and/or may act as effectors; (iii) apply advanced computational analyses to pinpoint biochemical and physiological functions of ucRBPs from large-scale data sets and the literature, and (iv) will explore the function of a selected subset of ucRBPs in greater detail. Together, these rapid and cost effective analyses will elucidate and validate the functions of ucRBPs, pave the way for mapping new regulatory mechanisms, identify potential functions for many human sequence variants, and will have broad impact on fields ranging from gene regulation to human genetics.