LARP1 specifically recognizes the 3′ terminus of poly(A) mRNA

•We purified specific RNPs by immunoprecipitation using a FLAG-tagged antisense LNA.•We identified the components of RNPs using an ultrasensitive mass spectrometry.•LARP1 specifically recognized the 3′ terminus of the poly(A) tail.•LARP1 stabilized mRNAs carrying a 5′ terminal oligopyrimidine tract (5′TOP). A poly(A) tail functions in mRNA turnover and in facilitating translation as a ribonucleoprotein complex with poly(A) binding proteins (PABPs). However, factors that associate with the poly(A) tail other than PABPs have not been described. Using proteomics, we identified candidate proteins that interact to the 3′ terminus of the poly(A) tail. Among these proteins, we focused on La motif-related protein 1 (LARP1) and found that LARP1 specifically recognizes the 3′ termini of normal poly(A) tails. We also reveal that LARP1 stabilizes multiple mRNAs carrying 5′ terminal oligopyrimidine tract (5′TOP). Our findings suggest that LARP1 may be involved in the post-transcriptional regulation of gene expression, at least in several 5′TOP mRNAs, through the binding to 3′ terminus of the poly(A) tail.