A novel exon generates ubiquitously expressed alternatively spliced new transcript of mouse Abcc4 gene.
Abcc4 gene codes for a protein (ABCC4) involved in the transportation of different classes of drugs outside the cells. Various important drugs transported by ABCC4 include antiviral and anticancer drugs as well as endogenous molecules such as bile acids, cyclic nucleotides, folates, prostaglandins and steroids. Alternative splicing generates multiple mRNAs that encode protein isoforms having diverse functions. In this study, we have identified a novel transcript of mouse Abcc4 gene using a combination of bioinformatics and molecular biology techniques. This transcript was found to be different from the reported transcript in having a different first exon that was found to be located on previously identified first intron. Newly identified transcript was found to be expressed across different tissues we studied and in different developmental stages. Expression level of novel and reported transcripts was studied using quantitative real-time PCR. After conceptually translating the novel transcript, various post-translational modifications were studied. Translation efficiency and predicted half life of encoded protein isoforms were analysed in silico. Molecular modelling was performed to compare the structural differences in both isoforms. The diversity at N-termini in these protein isoforms explains the diverse function of ABCC4 in mouse.
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
Sayeed Ur
SU
Rehman
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
Hassan Mubarak
HM
Ishqi
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
Mohammed Amir
MA
Husain
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India.
Tarique
T
Sarwar
Department of Biochemistry, Faculty of Life Sciences, A.M. University, Aligarh, U.P. 202002, India. Electronic address: tabish.bcmlab@gmail.com.
Mohammad
M
Tabish
D017398:Alternative Splicing / Q000502:physiology*; D000818:Animals; D005091:Exons / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C489540:Abcc4 protein, mouse
Abcc4 gene; Alternative splicing; Bioinformatics; Molecular biology; Mouse