Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast

Retrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1ΔN isoform to promote cell proliferation. Cdk2ap1ΔN functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1ΔN, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1ΔN expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.

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Non-canonical translation initiation in yeast generates a cryptic pool of mitochondrial proteins

Nucleic Acids Research ◽

10.1093/nar/gkz301 ◽

2019 ◽

Vol 47 (11) ◽

pp. 5777-5791 ◽

Cited By ~ 15

Author(s):

Geoffray Monteuuis ◽

Anna Miścicka ◽

Michał Świrski ◽

Lounis Zenad ◽

Olli Niemitalo ◽

...

Keyword(s):

Translation Initiation ◽

Single Gene ◽

Protein Isoforms ◽

Mitochondrial Proteins ◽

Mitochondrial Targeting ◽

Mitochondrial Proteome ◽

Alternative Protein ◽

Multiple Protein ◽

Translation Start ◽

Targeting Signal

Abstract Utilization of non-AUG alternative translation start sites is most common in bacteria and viruses, but it has been also reported in other organisms. This phenomenon increases proteome complexity by allowing expression of multiple protein isoforms from a single gene. In Saccharomyces cerevisiae, a few described cases concern proteins that are translated from upstream near-cognate start codons as N-terminally extended variants that localize to mitochondria. Using bioinformatics tools, we provide compelling evidence that in yeast the potential for producing alternative protein isoforms by non-AUG translation initiation is much more prevalent than previously anticipated and may apply to as many as a few thousand proteins. Several hundreds of candidates are predicted to gain a mitochondrial targeting signal (MTS), generating an unrecognized pool of mitochondrial proteins. We confirmed mitochondrial localization of a subset of proteins previously not identified as mitochondrial, whose standard forms do not carry an MTS. Our data highlight the potential of non-canonical translation initiation in expanding the capacity of the mitochondrial proteome and possibly also other cellular features.

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Recognition of CCA1 alternative protein isoforms during temperature acclimation

Plant Cell Reports ◽

10.1007/s00299-020-02644-7 ◽

2021 ◽

Author(s):

Shijia Zhang ◽

Huili Liu ◽

Li Yuan ◽

Xiaojing Li ◽

Lingbao Wang ◽

...

Keyword(s):

Temperature Acclimation ◽

Protein Isoforms ◽

Alternative Protein

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Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway

The Journal of Cell Biology ◽

10.1083/jcb.201909143 ◽

2020 ◽

Vol 219 (6) ◽

Author(s):

G. Lorenzo Odierna ◽

Sarah K. Kerwin ◽

Lucy E. Harris ◽

Grace Ji-eun Shin ◽

Nickolas A. Lavidis ◽

...

Keyword(s):

Motor Neurons ◽

Neuronal Development ◽

Surface Protein ◽

Synaptic Strength ◽

Protein Isoforms ◽

Synaptic Physiology ◽

Transmission Electron ◽

Alternative Protein ◽

A Cell ◽

And Function

Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons. We link the PI3K enhancer, Centaurin gamma 1A, to the Dscam2-dependent regulation of synaptic strength and show that changes in phosphoinositide levels correlate with changes in endosomal compartments that have previously been associated with synaptic strength. Using transmission electron microscopy, we find an increase in synaptic vesicles at Dscam2 mutant active zones, providing a rationale for the increase in synaptic strength. Our study provides the first evidence that Dscam2 can regulate synaptic physiology and highlights how diverse roles of alternative protein isoforms can contribute to unique aspects of brain development and function.

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Proteomics studies confirm the presence of alternative protein isoforms on a large scale

Genome Biology ◽

10.1186/gb-2008-9-11-r162 ◽

2008 ◽

Vol 9 (11) ◽

pp. R162 ◽

Cited By ~ 51

Author(s):

Michael L Tress ◽

Bernd Bodenmiller ◽

Ruedi Aebersold ◽

Alfonso Valencia

Keyword(s):

Large Scale ◽

Protein Isoforms ◽

Alternative Protein

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Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

10.1101/403543 ◽

2018 ◽

Author(s):

Wu Wei ◽

Bianca P. Hennig ◽

Jingwen Wang ◽

Yujie Zhang ◽

Ilaria Piazza ◽

...

Keyword(s):

Rna Degradation ◽

Chromatin Accessibility ◽

Protein Isoforms ◽

Transcription Start ◽

Mrna Isoforms ◽

Rna Molecules ◽

Transcription Start Sites ◽

Cryptic Transcription ◽

Functional Consequences ◽

Cryptic Promoters

AbstractCryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site usage, chromatin organization and post-transcriptional consequences in Saccharomyces cerevisiae. We show that transcription start sites (TSSs) of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality and chromatin accessibility. We degine the 5’ and 3’ boundaries of cryptic transcripts and show that, contrary to RNA degradation-sensitive ones, they often overlap with the end of the gene thereby using the canonical polyadenylation site and associate to polyribosomes. We show that chromatin-sensitive cryptic transcripts can be recognized by ribosomes and may produce truncated polypeptides from downstream, in-frame start codons. Finally, we congirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic datasets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters are in fact alternative truncated mRNA isoforms. The expression of these chromatin-sensitive isoforms is conserved from yeast to human expanding the functional consequences of cryptic transcription and proteome complexity.

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Tubulin polymerization promoting protein (TPPP) ortholog from Suberites domuncula and comparative analysis of TPPP/p25 gene family

Biologia ◽

10.2478/s11756-010-0147-y ◽

2011 ◽

Vol 66 (1) ◽

Cited By ~ 3

Author(s):

Mauro Štifanić ◽

Renato Batel ◽

Werner Müller

Keyword(s):

Comparative Analysis ◽

Genomic Structure ◽

Protein Isoforms ◽

Tubulin Polymerization ◽

Vertebrate Lineage ◽

Suberites Domuncula ◽

Functional Studies ◽

Living Fossils ◽

Alternative Protein ◽

Associated Proteins

AbstractSponges are one of the oldest metazoan phyla that are, due to their highly conservative nature, often referred to as the living fossils of multicellular animals. As such, they are a very important model for evolutionary, developmental and functional studies of Metazoa. Tubulin polymerization promoting proteins (TPPPs) are defined by the presence of p25-alpha domain (Pfam05517). Their functional characteristics resemble those of microtubule-associated proteins. Presence of TPPP homologous genes has been postulated in all eukaryotes with ciliated cells and their primary function has been proposed as some basic cilia-connected function. We present here the genomic structure and the corresponding cDNA sequence of one poriferan TPPP homolog (SdTPPP) isolated from the marine sponge Suberites domuncula; and a comparative analysis of TPPP homolog sequences and genomic structures from other Eukaryotes. Our results confirm the radiation of one TPPP homolog into three distinct genes in the Vertebrate lineage, but the origin of different sequences and their phylogenetic relationships show to be influenced by alternative protein isoforms, independent gene duplications, modularity of the p25-alpha domain and possible adaptational requirements to environmental conditions.

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Reconstructing protein and gene phylogenies using reconciliation and soft-clustering

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720017400078 ◽

2017 ◽

Vol 15 (06) ◽

pp. 1740007 ◽

Cited By ~ 4

Author(s):

Esaie Kuitche ◽

Manuel Lafond ◽

Aïda Ouangraoua

Keyword(s):

Phylogenetic Analyses ◽

Gene Tree ◽

Protein Product ◽

Species Tree ◽

Protein Isoforms ◽

Gene Trees ◽

Ensembl Database ◽

Reconstruction Methods ◽

Alternative Protein ◽

Protein Tree

The architecture of eukaryotic coding genes allows the production of several different protein isoforms by genes. Current gene phylogeny reconstruction methods make use of a single protein product per gene, ignoring information on alternative protein isoforms. These methods often lead to inaccurate gene tree reconstructions that require to be corrected before phylogenetic analyses. Here, we propose a new approach for the reconstruction of gene trees and protein trees accounting for alternative protein isoforms. We extend the concept of reconciliation to protein trees, and we define a new reconciliation problem called MinDRGT that consists in finding a gene tree that minimizes a double reconciliation cost with a given protein tree and a given species tree. We define a second problem called MinDRPGT that consists in finding a protein supertree and a gene tree minimizing a double reconciliation cost, given a species tree and a set of protein subtrees. We propose a shift from the traditional view of protein ortholog groups as hard-clusters to soft-clusters and we study the MinDRPGT problem under this assumption. We provide algorithmic exact and heuristic solutions for versions of the problems, and we present the results of applications on protein and gene trees from the Ensembl database. The implementations of the methods are available at https://github.com/UdeS-CoBIUS/Protein2GeneTree and https://github.com/UdeS-CoBIUS/SuperProteinTree .

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