Expression of Conjoined Genes: Another Mechanism for Gene Regulation in Eukaryotes

Abstract

From the ENCODE project, it is realized that almost every base of the entire human genome is transcribed. One class of transcripts resulting from this arises from the conjoined gene, which is formed by combining the exons of two or more distinct (parent) genes lying on the same strand of a chromosome. Only a very limited number of such genes are known, and the definition and terminologies used for them are highly variable in the public databases. In this work, we have computationally identified and manually curated 751 conjoined genes (CGs) in the human genome that are supported by at least one mRNA or EST sequence available in the NCBI database. 353 representative CGs, of which 291 (82%) could be confirmed, were subjected to experimental validation using RT-PCR and sequencing methods. We speculate that these genes are arising out of novel functional requirements and are not merely artifacts of transcription, since more than 70% of them are conserved in other vertebrate genomes. The unique splicing patterns exhibited by CGs reveal their possible roles in protein evolution or gene regulation. Novel CGs, for which no transcript is available, could be identified in 80% of randomly selected potential CG forming regions, indicating that their formation is a routine process. Formation of CGs is not only limited to human, as we have also identified 270 CGs in mouse and 227 in drosophila using our approach. Additionally, we propose a novel mechanism for the formation of CGs. Finally, we developed a database, ConjoinG, which contains detailed information about all the CGs (800 in total) identified in the human genome. In summary, our findings reveal new insights about the functionality of CGs in terms of another possible mechanism for gene regulation and genomic evolution and the mechanism leading to their formation.

The GOLD domain-containing protein TMED7 inhibits TLR4 signalling from the endosome upon LPS stimulation

“…It was originally reported that Tmed7 and Ticam2 (Tram) were two separate genes on chromosome 5; however, bioinformatics and experimental data have shown that there is a read-through from the Tmed7 gene into the Ticam2 gene, and this results in the expression of three genes, TMED7, TRAM and TAG 9,18 . Figure 1a demonstrates how TMED7, TRAM and TAG are generated.…”

“…We have previously reported that the TMED7 transcript occurs in a protein we named TRAM adaptor molecule with GOLD domain (TAG), owing to a read-through from the gene encoding tmed7 into the ticam2 gene on chromosome 5 9,17,18 . We now report that TMED7, like TAG 9 , acts as an inhibitor of the MyD88-independent TLR4 signalling pathway.…”

Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

“…Therefore, USP9Y-TTTY15 is a transcription-induced chimeric RNA (an RNA created in normal cells by combining exons from two or more distinctly known parental genes) (Akiva, 2005;Fang et al, 2012;Gingeras, 2009;Kannan et al, 2011;Kim DS et al, 2007Kim P et al, 2010;Kim RN et al, 2012;Li et al, 2008;Parra, 2005;Prakash et al, 2010;Thomson et al, 2000;Zhang et al, 2012). Linked to this finding, we also investigated the expression of another transcription-induced chimeric RNA previously studied in prostate cancer from Western countries, SLC45A3-ELK4, of which both partner genes lie on the same chromosome within a short genomic distance (1q32) (Maher et al, 2009;Rickman et al, 2009;Zhang et al, 2012).…”

Upregulation of INS-IGF2 read-through expression and identification of a novel INS-IGF2 splice variant in insulinomas

“…Recently, many chimeric RNAs where adjacent genes are fused have been identified (25,26). These fusion transcripts have been described by the terms 'gene read-through' and 'co-transcription and intergenic splicing' (27). Such read-through transcripts have been detected in different malignancies like prostate cancer (showing a SLC45A3-ELK4 transcript) (25,26) and melanoma (with a CDK2-RAB5B transcript) (28).…”

“…Such read-through transcripts have been detected in different malignancies like prostate cancer (showing a SLC45A3-ELK4 transcript) (25,26) and melanoma (with a CDK2-RAB5B transcript) (28). In addition to giving rise to new chimeric proteins or entirely novel proteins, read-through transcripts have been suggested to play a regulatory role by altering the expression of the parent genes (27).…”