Single molecule poly(A) tail-seq shows LARP4 opposes deadenylation through mRNA lifespan with most impact on short tails.

La-related protein 4 directly binds both poly(A) and poly(A)-binding protein (PABP). was shown to promote poly(A) tail (PAT) lengthening and stabilization of individual mRNAs presumably by protection from deadenylation (Mattijssen et al., 2017). We developed a nucleotide resolution transcriptome-wide, single molecule SM-PAT-seq method. This revealed Lduanyu374 effects on a wide range of PAT lengths for human mRNAs and mouse mRNAs from Lduanyu374 knockout (KO) and control cells. Lduanyu374 effects are clear on long PAT mRNAs but become more prominent at 30-75 nucleotides. We also analyzed time courses of PAT decay transcriptome-wide and for ~200 immune response mRNAs. This demonstrated accelerated deadenylation in KO cells on PATs <75 nucleotides and phasing features consistent with greater PABP dissociation in the absence of Thus, Lduanyu374 shapes PAT profiles throughout mRNA lifespan and with impact on mRNA decay at short lengths known to sensitize PABP dissociation in response to deadenylation machinery.

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