Poly(A) inclusive RNA isoform sequencing (PAIso−seq) reveals wide-spread non-adenosine residues within RNA poly(A) tails

Yusheng Liu, Hu Nie, Hongxiang Liu and Falong Lu ()
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Yusheng Liu: Chinese Academy of Sciences
Hu Nie: Chinese Academy of Sciences
Hongxiang Liu: Chinese Academy of Sciences
Falong Lu: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Message RNA poly(A) tails are vital for their function and regulation. However, the full-length sequence of mRNA isoforms with their poly(A) tails remains undetermined. Here, we develop a method at single-cell level sensitivity that enables quantification of poly(A) tails along with the full-length cDNA while reading non-adenosine residues within poly(A) tails precisely, which we name poly(A) inclusive RNA isoform sequencing (PAIso−seq). Using this method, we can quantify isoform specific poly(A) tail length. More interestingly, we find that 17% of the mRNAs harbor non-A residues within the body of poly(A) tails in mouse GV oocytes. We show that PAIso−seq is sensitive enough to analyze single GV oocytes. These findings will not only provide an accurate and sensitive tool in studying poly(A) tails, but also open a door for the function and regulation of non-adenosine modifications within the body of poly(A) tails.

Date: 2019
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DOI: 10.1038/s41467-019-13228-9

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