Difficulty in obtaining the complete mRNA coding sequence at 5'region (5'end mRNA artifact): Causes, consequences in biology and medicine and possible solutions for obtaining the actual amino acid sequence of proteins (Review).

Abstract

The known difficulty in obtaining the actual full length, complete sequence of a messenger RNA(mRNA) may lead to the erroneous determination of its coding sequence at the 5'region(5'end mRNA artifact), and consequently to the wrong assignment of the translation start codon, leading to the inaccurate prediction of the encoded polypeptide at its amino terminus. Among the known human genes whose study was affected by this artifact, we can include disco interacting protein2 homologA(DIP2A; KIAA0184), Down syndrome critical region1(DSCR1), SONDNA binding protein (SON), trefoil factor3(TFF3) and URB1 ribosome biogenesis1 homolog (URB1; KIAA0539) on chromosome21, aswellas receptor for activatedCkinase1(RACK1, also known as GNB2L1), glutaminyl‑tRNA synthetase(QARS) and tyrosyl-DNA phosphodiesterase2(TDP2) along with another 474loci, includinginterleukin16(IL16). In this review, we discuss the causes of this issue, its quantitative incidence in biomedical research, the consequences in biology and medicine, and the possible solutions for obtaining the actual amino acid sequence of proteins in the post-genomics era.