scholarly journals Trans-splicing of mRNAs links gene transcription to translational control regulated by mTOR

2018 ◽  
Author(s):  
Gemma Danks ◽  
Heloisa Galbiati ◽  
Martina Raasholm ◽  
Yamila N. Torres Cleuren ◽  
Eivind Valen ◽  
...  
Keyword(s):  
Gene Transcription ◽  
Growth Regulator ◽  
Translational Control ◽  
Oikopleura Dioica ◽  
Spliced Leader ◽  
Animal Density ◽  
Genome Wide ◽  
Trans Splicing ◽  
Initial Recovery ◽  
Favorable Conditions

AbstractIn phylogenetically diverse organisms, the 5’ ends of a subset of mRNAs are trans-spliced with a spliced leader (SL) RNA. The functions of SL trans-splicing, however, remain largely enigmatic. Here, we quantified translation genome-wide in the marine chordate, Oikopleura dioica, under inhibition of mTOR, a central growth regulator. Translation of trans-spliced TOP mRNAs was suppressed, showing that the SL sequence permits nutrient-dependent translational control of growth-related mRNAs. Under crowded, nutrient-limiting conditions, O. dioica continues to filter-feed, but arrests growth until favorable conditions return. Upon release from such conditions, initial recovery was independent of nutrient-responsive, trans-spliced genes, suggesting animal density sensing as a first trigger for resumption of development. Our results demonstrate a role for trans-splicing in the coordinated translational down-regulation of nutrient-responsive genes under limiting conditions.

scholarly journals Trans-splicing of mRNAs links gene transcription to translational control regulated by mTOR

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gemma B. Danks ◽  
Heloisa Galbiati ◽  
Martina Raasholm ◽  
Yamila N. Torres Cleuren ◽  
Eivind Valen ◽  
...  
Keyword(s):  
Growth Regulator ◽  
Translational Control ◽  
Oikopleura Dioica ◽  
Spliced Leader ◽  
Animal Density ◽  
Genome Wide ◽  
Trans Splicing ◽  
Initial Recovery ◽  
Favorable Conditions

Abstract Background In phylogenetically diverse organisms, the 5′ ends of a subset of mRNAs are trans-spliced with a spliced leader (SL) RNA. The functions of SL trans-splicing, however, remain largely enigmatic. Results We quantified translation genome-wide in the marine chordate, Oikopleura dioica, under inhibition of mTOR, a central growth regulator. Translation of trans-spliced TOP mRNAs was suppressed, consistent with a role of the SL sequence in nutrient-dependent translational control of growth-related mRNAs. Under crowded, nutrient-limiting conditions, O. dioica continued to filter-feed, but arrested growth until favorable conditions returned. Upon release from unfavorable conditions, initial recovery was independent of nutrient-responsive, trans-spliced genes, suggesting animal density sensing as a first trigger for resumption of development. Conclusion Our results are consistent with a proposed role of trans-splicing in the coordinated translational down-regulation of nutrient-responsive genes under growth-limiting conditions.

scholarly journals Spliced-Leader RNA trans Splicing in a Chordate, Oikopleura dioica, with a Compact Genome

2004 ◽  
Vol 24 (17) ◽  
pp. 7795-7805 ◽  
Author(s):  
Philippe Ganot ◽  
Torben Kallesøe ◽  
Richard Reinhardt ◽  
Daniel Chourrout ◽  
Eric M. Thompson
Keyword(s):  
Caenorhabditis Elegans ◽  
Regulatory Elements ◽  
Sm Proteins ◽  
Oikopleura Dioica ◽  
Spliced Leader ◽  
Trans Splicing ◽  
Spliced Leader Rna

ABSTRACT trans splicing of a spliced-leader RNA (SL RNA) to the 5′ ends of mRNAs has been shown to have a limited and sporadic distribution among eukaryotes. Within metazoans, only nematodes are known to process polycistronic pre-mRNAs, produced from operon units of transcription, into mature monocistronic mRNAs via an SL RNA trans-splicing mechanism. Here we demonstrate that a chordate with a highly compact genome, Oikopleura dioica, now joins Caenorhabditis elegans in coupling trans splicing with processing of polycistronic transcipts. We identified a single SL RNA which associates with Sm proteins and has a trimethyl guanosine cap structure reminiscent of spliceosomal snRNPs. The same SL RNA, estimated to be trans-spliced to at least 25% of O. dioica mRNAs, is used for the processing of both isolated or first cistrons and downstream cistrons in a polycistronic precursor. Remarkably, intercistronic regions in O. dioica are far more reduced than those in either nematodes or kinetoplastids, implying minimal cis-regulatory elements for coupling of 3′-end formation and trans splicing.

scholarly journals Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate

2017 ◽  
Author(s):  
Gemma B. Danks ◽  
Pavla Navratilova ◽  
Boris Lenhard ◽  
Eric Thompson
Keyword(s):  
Transcription Initiation ◽  
Core Promoter ◽  
Ribosomal Protein Genes ◽  
Oikopleura Dioica ◽  
Transcription Start Sites ◽  
Spliced Leader ◽  
Genome Wide ◽  
A Genome ◽  
Cap Analysis ◽  
Male Specific

AbstractDevelopment is largely driven by transitions between transcriptional programs. The initiation of transcription at appropriate sites in the genome is a key component of this and yet few rules governing selection are known. Here, we used cap analysis of gene expression (CAGE) to generate bp-resolution maps of transcription start sites (TSSs) across the genome of Oikopleura dioica, a member of the closest living relatives to vertebrates. Our TSS maps revealed promoter features in common with vertebrates, as well as striking differences, and uncovered key roles for core promoter elements in the regulation of development. During spermatogenesis there is a genome-wide shift in mode of transcription initiation characterized by a novel core promoter element. This element was associated with > 70% of transcription in the testis, including the male-specific use of cryptic internal promoters within operons. In many cases this led to the exclusion of trans-splice sites, revealing a novel mechanism for regulating which mRNAs receive the spliced leader. During oogenesis the cell cycle regulator, E2F1, has been co-opted in regulating maternal transcription in endocycling nurse nuclei. In addition, maternal promoters lack the TATA-like element found in vertebrates and have broad, rather than sharp, architectures with ordered nucleosomes. Promoters of ribosomal protein genes lack the highly conserved TCT initiator. We also report an association between DNA methylation on transcribed gene bodies and the TATA-box, which indicates that this ancient promoter motif may play a role in selecting DNA for transcription-associated methylation in invertebrate genomes.

scholarly journals An in vivo genetic screen for genes involved in spliced leader trans-splicing indicates a crucial role for continuous de novo spliced leader RNP assembly

2017 ◽  
Vol 45 (14) ◽  
pp. 8474-8483 ◽  
Author(s):  
Lucas Philippe ◽  
George C. Pandarakalam ◽  
Rotimi Fasimoye ◽  
Neale Harrison ◽  
Bernadette Connolly ◽  
...  
Keyword(s):  
Crucial Role ◽  
De Novo ◽  
Genetic Screen ◽  
Spliced Leader ◽  
Trans Splicing

scholarly journals A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni

2013 ◽  
Vol 108 (6) ◽  
pp. 707-717 ◽  
Author(s):  
Marina de Moraes Mourao ◽  
Maina Bitar ◽  
Francisco Pereira Lobo ◽  
Ana Paula Peconick ◽  
Priscila Grynberg ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Leader Sequence ◽  
Spliced Leader ◽  
Trans Splicing

scholarly journals Improved ribosome-footprint and mRNA measurements provide insights into dynamics and regulation of yeast translation

2015 ◽  
Author(s):  
David E Weinberg ◽  
Premal Shah ◽  
Stephen W Eichhorn ◽  
Jeffrey A Hussmann ◽  
Joshua B Plotkin ◽  
...  
Keyword(s):  
Translational Control ◽  
Nucleotide Composition ◽  
Ribosome Profiling ◽  
Open Reading Frames ◽  
Untranslated Regions ◽  
Coding Regions ◽  
Genome Wide ◽  
Upstream Open Reading Frames ◽  
Improved Methods ◽  
Reading Frames

Ribosome-footprint profiling provides genome-wide snapshots of translation, but technical challenges can confound its analysis. Here, we use improved methods to obtain ribosome-footprint profiles and mRNA abundances that more faithfully reflect gene expression in Saccharomyces cerevisiae. Our results support proposals that both the beginning of coding regions and codons matching rare tRNAs are more slowly translated. They also indicate that emergent polypeptides with as few as three basic residues within a 10-residue window tend to slow translation. With the improved mRNA measurements, the variation attributable to translational control in exponentially growing yeast was less than previously reported, and most of this variation could be predicted with a simple model that considered mRNA abundance, upstream open reading frames, cap-proximal structure and nucleotide composition, and lengths of the coding and 5′- untranslated regions. Collectively, our results reveal key features of translational control in yeast and provide a framework for executing and interpreting ribosome- profiling studies.

scholarly journals Intricate genetic programs controlling dormancy in Mycobacterium tuberculosis

2019 ◽  
Author(s):  
Abrar A. Abidi ◽  
Eliza J. R. Peterson ◽  
Mario L. Arrieta-Ortiz ◽  
Boris Aguilar ◽  
James T. Yurkovich ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Time Course ◽  
Experimental System ◽  
Topology Analysis ◽  
Transcriptional Dynamics ◽  
Regulatory Circuits ◽  
Genome Wide ◽  
Gene Regulatory ◽  
Location Map ◽  
Favorable Conditions

AbstractMycobacterium tuberculosis (MTB), responsible for the deadliest infectious disease worldwide, displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and opportunistically exploit immunocompromised individuals. Uncovering the gene regulatory programs that underlie the dramatic phenotypic shifts in MTB during disease latency and reactivation has posed an extraordinary challenge. We developed a novel experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the chain of transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding location map and insights from network topology analysis, we identified regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions.One Sentence SummaryHigh-resolution transcriptional time-course reveals six-state genetic program that enables MTB to enter and exit hypoxia-induced dormancy.

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