Top-ranked expressed gene transcripts of human protein-coding genes investigated with GTEx dataset

Abstract

With considerable accumulation of RNA-Seq transcriptome data, we have extended our understanding about protein-coding gene transcript compositions. However, alternatively compounded patterns of human protein-coding gene transcripts would complicate gene expression data processing and interpretation. It is essential to exhaustively interrogate complex mRNA isoforms of protein-coding genes with an unified data resource. In order to investigate representative mRNA transcript isoforms to be utilized as transcriptome analysis references, we utilized GTEx data to establish a top-ranked transcript isoform expression data resource for human protein-coding genes. Distinctive tissue specific expression profiles and modulations could be observed for individual top-ranked transcripts of protein-coding genes. Protein-coding transcripts or genes do occupy much higher expression fraction in transcriptome data. In addition, top-ranked transcripts are the dominantly expressed ones in various normal tissues. Intriguingly, some of the top-ranked transcripts are noncoding splicing isoforms, which imply diverse gene regulation mechanisms. Comprehensive investigation on the tissue expression patterns of top-ranked transcript isoforms is crucial. Thus, we established a web tool to examine top-ranked transcript isoforms in various human normal tissue types, which provides concise transcript information and easy-to-use graphical user interfaces. Investigation of top-ranked transcript isoforms would contribute understanding on the functional significance of distinctive alternatively spliced transcript isoforms.

The RNA methyltransferase METTL8 installs m3C32 in mitochondrial tRNAsThr/Ser(UCN) to optimise tRNA structure and mitochondrial translation

“…1a ), however, the two most common transcripts expressed in HEK293 cells only differ in the sequences encoding the protein C-terminus (Supplementary Fig. 1a, b ; Supplementary Table 1 ) and the mRNA encoding the full-length (407 amino acid) protein is the top-ranked isoform in most human tissues 44 . To explore the sub-cellular localisation of the longest METTL8 isoform, a stably transfected HEK293 cell line for the tetracycline-inducible expression of C-terminally GFP tagged METTL8 (METTL8-GFP) was generated.…”

Uncovering the impacts of alternative splicing on the proteome with current omics techniques

“…One or more alternative splicing events can give rise to a wide range of transcript-isoform outputs, from two to a few hundred per gene (Ray et al, 2020;Tung et al, 2020), leading to complex patterns of coordinate splicing events BOX 1 Computational approaches for alternative splicing detection Genome-wide detection of alternative splicing (AS) can be based on full-length isoforms, exons, exon-exon junctions, or events. Isoform-based methods use transcript abundances to calculate differential transcript usage (DTU), as in Cuffdiff2 from the Cufflinks package (Trapnell et al, 2010) or SUPPA (Alamancos et al, 2015;Trincado et al, 2018), or isoform switches, as in iso-kTSP (Sebestyén et al, 2015).…”

Molecular Modelling Hurdle in the Next-Generation Sequencing Era

“…From the 54 tissues from GTEx, the switch from the predominant isoform to another in one tissue happens in approximately 1000 genes (Figure 5C). Tung et al [13] analyzed up to four tissue switches, highlighting the relevance of this phenomenon. MECP2 has two main transcripts (Figure 6A, Supplementary Table S3), and it is shown as an example of a gene with a high-order transcript switch, with 14 tissue switches (Figure 6B).…”