It has been proposed that Ataxin-2, a member of the LSm protein family, participates in the regulation of RNA metabolism through interaction with PABPC1. However, the exact biological mechanism and in vivo targets remain unknown. Moreover, abnormal expansion of polyglutamine (polyQ) in the human-specific polyQ domain of Ataxin-2 to more than 34 repeats leads to spinocerebellar ataxia type 2 (SCA2), whereas intermediate polyQ expansion (27–33 repeats) is associated with risk for amyotrophic lateral sclerosis (ALS), suggesting a common pathogenetic role for Ataxin-2 in both neurodegenerative diseases. Here we report that Ataxin-2 binds directly to RNAs in a PABPC1-independent manner. High-throughput sequencing of Ataxin-2-bound RNAs prepared by PAR-CLIP revealed that Ataxin-2 binds predominantly to uridine-rich elements, including well-characterized cis-regulatory AU-rich elements, in the 3’UTRs of target mRNAs. Gene expression analysis after Ataxin-2 depletion or overexpression revealed that Ataxin-2 stabilizes target mRNAs and increases the abundance of corresponding proteins. These findings suggest that Ataxin-2 is an RNA-binding protein that targets cis-regulatory elements in 3’UTRs to stabilize a subset of mRNAs and increase protein expression. We also found that disease-associated polyQ expansion downregulates the physiological activity of Ataxin-2. This evidence indicates that loss of Ataxin-2 function might play a causative role in the pathogenesis of neurodegeneration, at least in part.