Coupled and independent functions of PABPN1 in RNA processing revealed by direct RNA nanopore sequencing

Poly(A) Binding Protein Nuclear 1 (PABPN1), a nuclear protein, is renowned for its role in promoting poly(A) tail synthesis. However, recent research has revealed that PABPN1 is involved in various other RNA processing functions, which were previously studied separately. To better understand the combined and individual roles of PABPN1 in RNA processing, researchers employed a combination of loss-of-function experiments, cellular fractionation, and direct RNA nanopore sequencing.

The findings of this study demonstrate that PABPN1 depletion leads to distinct effects on alternative polyadenylation, nuclear-to-cytoplasmic mRNA trafficking, and long non-coding RNA distribution, depending on the specific transcript. Surprisingly, PABPN1 deficiency also enhances splicing in thousands of pre-mRNAs and alters the abundance of N6-methyladenosine in the cytoplasm, expanding the diverse roles of this protein.

While PABPN1 depletion results in a global shortening of poly(A) tails in most genes, other functions of PABPN1 affect different groups of genes and are not directly related to one another. However, some of these groups share common characteristics, such as longer poly(A) tails and proximity to nuclear speckles in control cells.

Overall, these results highlight the crucial role of PABPN1 in post-transcriptional gene regulation, influencing the identity, localization, and abundance of thousands of coding and non-coding RNAs.