mountainClimber Identifies Alternative Transcription Start and Polyadenylation Sites in RNA-Seq

AbstractAs more and larger genomics studies appear, there is a growing need for comprehensive and queryable cross-study summaries. Snaptron is a search engine for summarized RNA sequencing data with a query planner that leverages R-tree, B-tree and inverted indexing strategies to rapidly execute queries over 146 million exon-exon splice junctions from over 70,000 human RNA-seq samples. Queries can be tailored by constraining which junctions and samples to consider. Snaptron can also rank and score junctions according to tissue specificity or other criteria. Further, Snaptron can rank and score samples according to the relative frequency of different splicing patterns. We outline biological questions that can be explored with Snaptron queries, including a study of novel exons in annotated genes, of exonization of repetitive element loci, and of a recently discovered alternative transcription start site for the ALK gene. Web app and documentation are at http://snaptron.cs.jhu.edu. Source code is at https://github.com/ChristopherWilks/snaptron under the MIT license.

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Properties of an Intergenic Terminator and Start Site Switch That Regulate IMD2 Transcription in Yeast

Molecular and Cellular Biology ◽

10.1128/mcb.00380-08 ◽

2008 ◽

Vol 28 (12) ◽

pp. 3883-3893 ◽

Cited By ~ 60

Author(s):

M. Harley Jenks ◽

Thomas W. O'Rourke ◽

Daniel Reines

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Initiation Site ◽

Start Codon ◽

Start Site ◽

Transcription Start ◽

Transcription Start Sites ◽

Short Transcript ◽

Alternative Transcription ◽

Polyadenylation Sites

ABSTRACT The IMD2 gene in Saccharomyces cerevisiae is regulated by intracellular guanine nucleotides. Regulation is exerted through the choice of alternative transcription start sites that results in synthesis of either an unstable short transcript terminating upstream of the start codon or a full-length productive IMD2 mRNA. Start site selection is dictated by the intracellular guanine nucleotide levels. Here we have mapped the polyadenylation sites of the upstream, unstable short transcripts that form a heterogeneous family of RNAs of ≈200 nucleotides. The switch from the upstream to downstream start sites required the Rpb9 subunit of RNA polymerase II. The enzyme's ability to locate the downstream initiation site decreased exponentially as the start was moved downstream from the TATA box. This suggests that RNA polymerase II's pincer grip is important as it slides on DNA in search of a start site. Exosome degradation of the upstream transcripts was highly dependent upon the distance between the terminator and promoter. Similarly, termination was dependent upon the Sen1 helicase when close to the promoter. These findings extend the emerging concept that distinct modes of termination by RNA polymerase II exist and that the distance of the terminator from the promoter, as well as its sequence, is important for the pathway chosen.

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Principles for RNA metabolism and alternative transcription initiation within closely spaced promoters

10.1101/055731 ◽

2016 ◽

Author(s):

Yun Chen ◽

Athma A. Pai ◽

Jan Herudek ◽

Michal Lubas ◽

Nicola Meola ◽

...

Keyword(s):

Transcription Initiation ◽

Core Promoter ◽

Building Blocks ◽

Gene Promoters ◽

Mrna Transcription ◽

Transcription Start ◽

Transcription Start Sites ◽

Alternative Transcription ◽

Mammalian Genomes ◽

Polyadenylation Sites

AbstractMammalian transcriptomes are complex and formed by extensive promoter activity. In addition, gene promoters are largely divergent and initiate transcription of reverse-oriented promoter upstream transcripts (PROMPTs). Although PROMPTs are commonly terminated early, influenced by polyadenylation sites, promoters often cluster so that the divergent activity of one might impact another. Here, we find that the distance between promoters strongly correlates with the expression, stability and length of their associated PROMPTs. Adjacent promoters driving divergent mRNA transcription support PROMPT formation, but due to polyadenylation site constraints, these transcripts tend to spread into the neighboring mRNA on the same strand. This mechanism to derive new alternative mRNA transcription start sites (TSSs) is also evident at closely spaced promoters supporting convergent mRNA transcription. We suggest that basic building blocks of divergently transcribed core promoter pairs, in combination with the wealth of TSSs in mammalian genomes, provides a framework with which evolution shapes transcriptomes.

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Aptardi predicts polyadenylation sites in sample-specific transcriptomes using high-throughput RNA sequencing and DNA sequence

Nature Communications ◽

10.1038/s41467-021-21894-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ryan Lusk ◽

Evan Stene ◽

Farnoush Banaei-Kashani ◽

Boris Tabakoff ◽

Katerina Kechris ◽

...

Keyword(s):

Rna Sequencing ◽

Dna Sequence ◽

Mammalian Species ◽

Alternative Polyadenylation ◽

Sequence Information ◽

Rna Seq ◽

Average Precision ◽

Polyadenylation Sites ◽

Dna Nucleotide Sequence

AbstractAnnotation of polyadenylation sites from short-read RNA sequencing alone is a challenging computational task. Other algorithms rooted in DNA sequence predict potential polyadenylation sites; however, in vivo expression of a particular site varies based on a myriad of conditions. Here, we introduce aptardi (alternative polyadenylation transcriptome analysis from RNA-Seq data and DNA sequence information), which leverages both DNA sequence and RNA sequencing in a machine learning paradigm to predict expressed polyadenylation sites. Specifically, as input aptardi takes DNA nucleotide sequence, genome-aligned RNA-Seq data, and an initial transcriptome. The program evaluates these initial transcripts to identify expressed polyadenylation sites in the biological sample and refines transcript 3′-ends accordingly. The average precision of the aptardi model is twice that of a standard transcriptome assembler. In particular, the recall of the aptardi model (the proportion of true polyadenylation sites detected by the algorithm) is improved by over three-fold. Also, the model—trained using the Human Brain Reference RNA commercial standard—performs well when applied to RNA-sequencing samples from different tissues and different mammalian species. Finally, aptardi’s input is simple to compile and its output is easily amenable to downstream analyses such as quantitation and differential expression.

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Expression of murine muscle-enriched A-type lamin-interacting protein (MLIP) is regulated by tissue-specific alternative transcription start sites

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.003758 ◽

2018 ◽

Vol 293 (51) ◽

pp. 19761-19770

Author(s):

Marie-Elodie Cattin ◽

Shelley A. Deeke ◽

Sarah A. Dick ◽

Zachary J. A. Verret-Borsos ◽

Gayashan Tennakoon ◽

...

Keyword(s):

Transcription Start ◽

Interacting Protein ◽

Tissue Specific ◽

Transcription Start Sites ◽

Alternative Transcription ◽

Specific Alternative

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Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

Frontiers in Endocrinology ◽

10.3389/fendo.2021.690648 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yoshifumi Kasuga ◽

Tomoko Kawai ◽

Kei Miyakoshi ◽

Yoshifumi Saisho ◽

Masumi Tamagawa ◽

...

Keyword(s):

Diabetes Mellitus ◽

Dna Methylation ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Start Site ◽

Epigenetic Changes ◽

Neonatal Hypoglycaemia ◽

Transcription Start ◽

Cpg Sites ◽

Alternative Transcription

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

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