Ranked Choice Voting for Representative Transcripts with TRaCE

Genome sequencing projects annotate protein-coding gene models with multiple transcripts, aiming to represent all of the available transcript evidence. However, downstream analyses often operate on only one representative transcript per gene locus, sometimes known as the canonical transcript. To choose canonical transcripts, TRaCE (Transcript Ranking and Canonical Election) holds an 'election' in which a set of RNA-seq samples rank transcripts by annotation edit distance. These sample-specific votes are tallied along with other criteria such as protein length and InterPro domain coverage. The winner is selected as the canonical transcript, but the election proceeds through multiple rounds of voting to order all the transcripts by relevance. Based on the set of expression data provided, TRaCE can identify the most common isoforms from a broad expression atlas or prioritize alternative transcripts expressed in specific contexts.

VarMap: a web tool for mapping genomic coordinates to protein sequence and structure and retrieving protein structural annotations

Motivation Understanding the protein structural context and patterning on proteins of genomic variants can help to separate benign from pathogenic variants and reveal molecular consequences. However, mapping genomic coordinates to protein structures is non-trivial, complicated by alternative splicing and transcript evidence. Results Here we present VarMap, a web tool for mapping a list of chromosome coordinates to canonical UniProt sequences and associated protein 3D structures, including validation checks, and annotating them with structural information. Availability and implementation https://www.ebi.ac.uk/thornton-srv/databases/VarMap. Supplementary information Supplementary data are available at Bioinformatics online.

Role of the Transcription Activator Ste12p as a Repressor of PRY3 Expression

ABSTRACT Mating pheromone represses synthesis of full-length PRY3 mRNA, and a new transcript appears simultaneously with its 5′ terminus 452 nucleotides inside the open reading frame (ORF). Synthesis of this shorter transcript results from activation of a promoter within the PRY3 locus, and its production is concomitant with the rapid disappearance of the full-length transcript. Evidence is consistent with the pheromone-induced transcription factor Ste12p binding two pheromone response elements within the PRY3 promoter, directly impeding transcription of the full-length mRNA while simultaneously inducing initiation of the short transcript. This process depends on a TATA box within the PRY3 ORF. Expression of full-length PRY3 inhibited mating, while no disadvantage was detectable for cells unable to make the short transcript. Therefore, Ste12p is utilized as a repressor of full-length PRY3 transcription, ensuring efficient mating. There is no evidence that production of the short PRY3 transcript is anything more than an adventitious by-product of this mechanism. It is possible that cryptic binding sites for transcriptional activators may occur frequently within genomes and have the potential of evolving for rapid, gene-specific repression by mechanisms analogous to PRY3. PRY3 regulation provides a model for the coordination of both inductive and repressive activities within a regulatory network.

A novel mechanism of self-primed reverse transcription defines a new family of retroelements.

Retroviruses and long terminal repeat (LTR)-containing retrotransposons initiate reverse transcription by using a specific tRNA primer than anneals to the primer-binding site of the retroelement transcript. Sequences from a large number of retroviruses and LTR-containing retrotransposons had indicated that the role of tRNAs in priming reverse transcription is universal among these LTR-containing retroelements. Data presented here strongly support the surprising conclusion that Tf1, a highly active LTR-containing retrotransposon isolated from Schizosaccharomyces pombe, undergoes a novel self-priming process that requires hybridization between the primer-binding site and the first 11 bases of the Tf1 transcript. Single-base mutations in these regions block transposition and reverse transcription, while compensatory mutations that reestablish complementarily rescue both defects. In addition, the sequence of the minus-strand RNA primer of reverse transcription was consistent with its being derived from the 5' end of the Tf1 transcript. Evidence that this mechanism defines a new family of retroelements is presented.