TY - GEN
T1 - A novel signature for identification of upstream alternative translation initiation sites
AU - Karri, Kritika
AU - Bastola, Dhundy R.
PY - 2015/12/16
Y1 - 2015/12/16
N2 - Alternative translation initiation sites (aTIS) and the factors that determine an ideal mode of translation of mRNA in the eukaryotic system has been widely studied over the past several decades. Such studies demonstrate that single mRNA can yield multiple protein isoforms using the AUG and non-AUG start codons. While the conspicuous scanning model explains how the process of translation initiation begins when the pre-initiation complex encounters a start codon with optimal sequence context, referred to as "Kozak" consensus and the leaky scanning model explains the process of alternative translation downstream. Additionally, there are alternative translation initiation sites upstream and in-frame to the canonical AUG start site, which are present in the 5′ UTR of the mRNA. This choice of aTIS results in a longer N-terminally expanded protein isoform. It is unclear as to what are the factors that determine the selection of a start codon to be a potential upstream aTIS. In this study we investigate if there exists a third element, besides the sequence context at a certain distance from canonical AUG start codon, in the 5′ UTR of human mRNAs called the "complementary matching palindrome" that differentiates an upstream aTIS from any other codon. Our results show the presence of longest complementary matching palindrome around CUG codon, which may serve as an aTIS to translate proteins that are longer than their canonical isoforms.
AB - Alternative translation initiation sites (aTIS) and the factors that determine an ideal mode of translation of mRNA in the eukaryotic system has been widely studied over the past several decades. Such studies demonstrate that single mRNA can yield multiple protein isoforms using the AUG and non-AUG start codons. While the conspicuous scanning model explains how the process of translation initiation begins when the pre-initiation complex encounters a start codon with optimal sequence context, referred to as "Kozak" consensus and the leaky scanning model explains the process of alternative translation downstream. Additionally, there are alternative translation initiation sites upstream and in-frame to the canonical AUG start site, which are present in the 5′ UTR of the mRNA. This choice of aTIS results in a longer N-terminally expanded protein isoform. It is unclear as to what are the factors that determine the selection of a start codon to be a potential upstream aTIS. In this study we investigate if there exists a third element, besides the sequence context at a certain distance from canonical AUG start codon, in the 5′ UTR of human mRNAs called the "complementary matching palindrome" that differentiates an upstream aTIS from any other codon. Our results show the presence of longest complementary matching palindrome around CUG codon, which may serve as an aTIS to translate proteins that are longer than their canonical isoforms.
KW - 5′ UTR
KW - Complementary matching palindrome
KW - aTIS (alternative Translation Initiation Site)
KW - uORF
UR - http://www.scopus.com/inward/record.url?scp=84962339468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962339468&partnerID=8YFLogxK
U2 - 10.1109/BIBM.2015.7359850
DO - 10.1109/BIBM.2015.7359850
M3 - Conference contribution
AN - SCOPUS:84962339468
T3 - Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
SP - 1184
EP - 1191
BT - Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
A2 - Schapranow, lng. Matthieu
A2 - Zhou, Jiayu
A2 - Hu, Xiaohua Tony
A2 - Ma, Bin
A2 - Rajasekaran, Sanguthevar
A2 - Miyano, Satoru
A2 - Yoo, Illhoi
A2 - Pierce, Brian
A2 - Shehu, Amarda
A2 - Gombar, Vijay K.
A2 - Chen, Brian
A2 - Pai, Vinay
A2 - Huan, Jun
PB - Institute of Electrical and Electronics Engineers Inc.
T2 - IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
Y2 - 9 November 2015 through 12 November 2015
ER -