Abstract
The human E74-like ETS transcription factor 3 (Elf-3) is an epithelium-specific member of the ETS family, all members of which are characterized by a highly conserved DNA-binding domain. Elf-3 plays a crucial role in epithelial cell differentiation by participating in morphogenesis and terminal differentiation of the murine small intestinal epithelium, and also acts as an indispensable regulator of mesenchymal to epithelial transition, underlying its significant involvement in development and in pathological states, such as cancer. Although previous research works have deciphered the functional role of Elf-3 in normal physiology as well as in tumorigenesis, the present study highlights for the first time the wide spectrum of ELF3 mRNAs that are transcribed, providing an in-depth analysis of splicing events and exon/intron boundaries in a broad panel of human cell lines. The implementation of a versatile targeted nanopore sequencing approach led to the identification of 25 novel ELF3 mRNA transcript variants (ELF3 v.3–v.27) with new alternative splicing events, as well as two novel exons. Although the current study provides a qualitative transcriptional profile regarding ELF3, further studies must be conducted, so the biological function of all novel alternative transcript variants as well as the putative protein isoforms are elucidated.
Highlights
Alternative splicing (AS) constitutes a tightly regulated mechanism of eukaryotic cells that ensures their essential transcriptomic and proteomic diversity by producing multiple mRNA transcripts from a single gene [1]
Nanopore Sequencing Reveals New Alternative Splicing Events of ELF3. Both the computational analysis with our algorithm ASDT as well as the visualization of the successfully aligned reads with Integrative Genomics Viewer (IGV), confirmed the existence of all annotated splice junctions that are present in the annotated ELF3 protein-coding transcripts v.1 and v.2 (GenBank® accession numbers: NM_004433.5 and NM_001114309.2, respectively)
Besides the detection of the annotated ELF3 transcripts the computational analysis led to the identification of novel, less abundant ELF3 mRNA transcripts, which contain new alternative splicing events, as well as two novel exons
Summary
Alternative splicing (AS) constitutes a tightly regulated mechanism of eukaryotic cells that ensures their essential transcriptomic and proteomic diversity by producing multiple mRNA transcripts from a single gene [1]. During the process of AS, a megadalton machinery known as the spliceosome excises the intronic sequences of the precursor mRNAs (pre-mRNAs) and subsequently joins the exons together to generate mature mRNAs. Genome-wide studies have revealed that the overwhelming majority (~95%) of pre-mRNAs undergo AS, generating a covey of transcripts with differential structural and functional features [1,3]. The produced alternative splice variants may exhibit differential protein-coding capacities, subcellular localizations, stability and functional roles [5]. Changes in the alternative splicing mechanism subserve the development of cancer-associated phenotypes by promoting angiogenesis [10], avoiding apoptosis [11] and inducing cell proliferation [12], invasion and metastasis [13,14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
