RNA tailing (nontemplated nucleotide addition to the 3′ end of RNA) is one of the most frequent type of RNA modification. Terminal nucleotidyl transferases (TNTs) catalyze RNA tailing reaction, and thereby affects critically the biogenesis, stability and activity of RNAs. To understand the function of RNA tailing at the genomic scale, we have developed a method termed TAIL-seq which determines poly(A) tail length and 3’ end modifications simultaneously. Using this method, we found widespread uridylation and guanylation on mRNAs. TNT4/7 promotes mRNA turnover by generating an oligo(U) tail which serves as a general mark for mRNA decay. We also discover recently that a subset of TNTs carry out guanylation to shield mRNA from deadenylation. In this presentation, I will discuss the regulatory role and action mechanism of RNA tailing machinery.