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

Danks, Gemma B.; Galbiati, Heloisa; Raasholm, Martina; Cleuren, Yamila N. Torres; Valen, Eivind; Navrátilová, Pavla; Thompson, Eric M.

doi:10.1186/s12864-019-6277-x

Cited by 3 publications

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is consistent with in vitro biochemical studies which have shown that transcripts beginning with a pyrimidine (C/T) have a lower affinity for eIF4E binding than those starting with a purine (A/G) (Meyuhas and Kahan, 2015;Tamarkin-Ben-Harush et al, 2017). An initial C is a feature of transcripts containing a 5 0 terminal oligo-pyrimidine (TOP) tract, a motif often present in mRNAs encoding the protein synthesis machinery and a target of mTOR-mediated translation control (Meyuhas and Kahan, 2015;Tamarkin-Ben-Harush et al, 2017;Danks et al, 2019). We found that while C has an effect, the overall effect on SE and TE reduction is dominated by mRNAs with the TOP motif (Figure 2G).…”

Section: A B D Csupporting

confidence: 86%

Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Section: A B D Csupporting

confidence: 86%

Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

slORFfinder: a tool to detect open reading frames resulting from trans-splicing of spliced leader sequences

Song

Jiang

et al. 2023

Briefings in Bioinformatics

View full text Add to dashboard Cite

Trans-splicing of a spliced leader (SL) to the 5′ ends of mRNAs is used to produce mature mRNAs in several phyla of great importance to human health and the marine ecosystem. One of the consequences of the addition of SL sequences is the change or disruption of the open reading frames (ORFs) in the recipient transcripts. Given that most SL sequences have one or more of the trinucleotide NUG, including AUG in flatworms, trans-splicing of SL sequences can potentially supply a start codon to create new ORFs, which we refer to as slORFs, in the recipient mRNAs. Due to the lack of a tool to precisely detect them, slORFs were usually neglected in previous studies. In this work, we present the tool slORFfinder, which automatically links the SL sequences to the recipient mRNAs at the trans-splicing sites identified from SL-containing reads of RNA-Seq and predicts slORFs according to the distribution of ribosome-protected footprints (RPFs) on the trans-spliced transcripts. By applying this tool to the analyses of nematodes, ascidians and euglena, whose RPFs are publicly available, we find wide existence of slORFs in these taxa. Furthermore, we find that slORFs are generally translated at higher levels than the annotated ORFs in the genomes, suggesting they might have important functions. Overall, this study provides a tool, slORFfinder (https://github.com/songbo446/slORFfinder), to identify slORFs, which can enhance our understanding of ORFs in taxa with SL machinery.

show abstract

Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution

Nguyen,

Sosa,

Cassidy

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

TOR (target of rapamycin), a ubiquitous protein kinase central to cellular homeostasis maintenance, fundamentally regulates ribosome biogenesis in part by its target La-related protein 1 (LARP1). Among other target transcripts, LARP1 specifically binds TOP (terminal oligopyrimidine) mRNAs encoding all 80 ribosomal proteins in a TOR-dependent manner through its C-terminal region containing the DM15 module. Though the functional implications of the LARP1 interaction with target mRNAs is controversial, it is clear that the TOP-LARP1-TOR axis is critical to cellular health in humans. Its existence and role in evolutionarily divergent animals remain less understood. We focused our work on expanding our knowledge of the first arm of the axis: the connection between LARP1-DM15 and the 5’ TOP motif. We show that the overall DM15 architecture observed in humans is conserved in fruit fly and zebrafish. Both adopt familiar curved arrangements of HEAT-like repeats that bind 5’ TOP mRNAs on the same conserved surface, although molecular dynamics simulations suggest that the N-terminal fold of the fruit fly DM15 is predicted to be unstable and unfold. We demonstrate that each ortholog interacts with TOP sequences with varying affinities. Importantly, we determine that the ability of the DM15 region to bind some TOP sequences but not others might amount to the context of the RNA structure, rather than the ability of the module to recognize some sequences but not others. We propose that TOP mRNAs may retain similar secondary structures to regulate LARP1 DM15 recognition.

show abstract

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

Cited by 3 publications

References 30 publications

Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation

Profiling of Small Ribosomal Subunits Reveals Modes and Regulation of Translation Initiation

slORFfinder: a tool to detect open reading frames resulting from trans-splicing of spliced leader sequences

Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution

Contact Info

Product

Resources

About