Genome-wide identification of cancer-related polyadenylated and non-polyadenylated RNAs in human breast and lung cell lines

Guoguang Zhao,Kuntao Yu,Liang Sun,Hui Li,Runsheng Chen,Haitao Luo,Dechao Bu,Fei Jiao,Yi Zhao,Qi Liao

doi:10.1007/s11427-013-4485-1

Abstract

Eukaryotic mRNAs consist of two forms of transcripts: poly(A)+ and poly(A)-, based on the presence or absence of poly(A) tails at the 3' end. Poly(A)+ mRNAs are mainly protein coding mRNAs, whereas the functions of poly(A)- mRNA are largely unknown. Previous studies have shown that a significant proportion of gene transcripts are poly(A)- or bimorphic (containing both poly(A)+ and poly(A)- transcripts). We compared the expression levels of poly(A)- and poly(A)+ RNA mRNAs in normal and cancer cell lines. We also investigated the potential functions of these RNA transcripts using an integrative workflow to explore poly(A)+ and poly(A)- transcriptome sequences between a normal human mammary gland cell line (HMEC) and a breast cancer cell line (MCF-7), as well as between a normal human lung cell line (NHLF) and a lung cancer cell line (A549). The data showed that normal and cancer cell lines differentially express these two forms of mRNA. Gene ontology (GO) annotation analyses hinted at the functions of these two groups of transcripts and grouped the differentially expressed genes according to the form of their transcript. The data showed that cell cycle-, apoptosis-, and cell death-related functions corresponded to most of the differentially expressed genes in these two forms of transcripts, which were also associated with the cancers. Furthermore, translational elongation and translation functions were also found for the poly(A)- protein-coding genes in cancer cell lines. We demonstrate that poly(A)- transcripts play an important role in cancer development.

Highlights

Eukaryotic mRNAs consist of two forms of transcripts: poly(A)+ and poly(A), based on the presence or absence of poly(A) tails at the 3 end
We investigated the potential functions of these RNA transcripts using an integrative workflow to explore poly(A)+ and poly(A) transcriptome sequences between a normal human mammary gland cell line (HMEC) and a breast cancer cell line (MCF-7), as well as between a normal human lung cell line (NHLF) and a lung cancer cell line (A549)
Our study provided several important observations: (i) the transcripts of some annotated coding genes were in the poly(A) form; (ii) according to their relative abundance (FPKM values), all expressed transcripts could be divided into three subgroups: poly(A)+, poly(A) and bimorphic; (iii) half (50.0% on average in these cell lines) of these expressed protein-coding transcripts were poly(A)+, while the other half were bimorphic (40%) or poly(A) (10%); and (iv) Gene ontology (GO) enrichment analyses showed that poly(A)+ and some poly(A) differentially expressed transcripts (DETs) were associated with cell cycle progression, DNA damage, and apoptosis-related genes, whereas poly(A) DETs were associated with gene translational elongation and translation functional categories, suggesting that poly(A)+ and poly(A) transcripts play different roles in tumor development and progression

Summary

Introduction

Eukaryotic mRNAs consist of two forms of transcripts: poly(A)+ and poly(A) , based on the presence or absence of poly(A) tails at the 3 end. We compared the expression levels of poly(A) and poly(A)+ RNA mRNAs in normal and cancer cell lines. The data showed that normal and cancer cell lines differentially express these two forms of mRNA. The majority of known mRNA transcripts are poly(A)+ [4], whereas the poly(A) forms usually encode ribosomal RNAS [5], histone RNAs [6], tRNAs, and certain small [7] and long non-coding RNAs [8]. There is a need to determine the levels of poly(A) or the bimorphic form of RNA expression and their functions in normal and cancerous cells to better understand the cell biology and mechanism of cancer development and progression. We identified the poly(A)+ and poly(A) transcripts in HMEC, MCF-7, NHLF, and A549 cell lines and explored their potential functions in human cancer. We analyzed eight RNA transcript datasets [13] representing poly(A)+ and poly(A) transcripts in the four human normal, adenocarcinoma breast and lung tissues cell lines

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Conclusion