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.