The splicing of tiny introns of Paramecium is controlled by MAGO

Mañero, Julia; Begley, Victoria; Marsella, Laura; Villalobo, Eduardo

doi:10.1016/j.gene.2018.04.007

Cited by 3 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S1D). Silencing of Magoh in Paramecium or knockout of Y14 in Y. lipolytica caused changes in intron retention, indicating a function in splicing (62, 63). We therefore analysed the T. brucei Y14/Magoh double knockout for splicing defects, by probing for exon and intron of the intron-containing mRNA DBP2B of T. brucei , with dual colour single molecule smFISH (56).…”

Section: Resultsmentioning

confidence: 99%

Intron-loss in Kinetoplastea correlates with a non-functional EJC and loss of NMD factors

Gabiatti,

Freire,

Odenwald

et al. 2024

Preprint

View full text Add to dashboard Cite

In metazoans, mRNA quality is tightly monitored from transcription to translation. A key role lies with the exon junction complex (EJC) that is placed upstream of the exon-exon junction after splicing. The EJC inner core is composed of Magoh, Y14, eIF4AIII and BTZ and the outer core of proteins involved in mRNA splicing (CWC22), export (Yra1), translation (PYM) and non-sense mediated decay (NMD, UPF1/2/3). The protozoan parasite Trypanosoma brucei encodes only two genes with introns, but all mRNAs are processed by trans-splicing. The presence of the three core EJC proteins and a potential BTZ homologue (Rbp25) in trypanosomes has been suggested as an adaptation of the EJC function to mark trans-spliced mRNAs. We analysed trypanosome EJC components and noticed major differences between eIF4AIII and Magoh/Y14: (i) whilst eIF4AIII is essential, knocking out both Magoh and Y14 elicits only a mild growth phenotype and does not affect processing, export or stability of the two cis-spliced mRNAs (ii) eIF4AIII localization is mostly nucleolar, with a minor proportion in the nucleoplasm and cytoplasm, while Magoh and Y14 are nucleolar and nucleoplasmic but excluded from the cytoplasm (iii) eIF4AIII associates with nucleolar proteins (including NOM1/Sgd1p) and the splicing factor CWC22, but not with Y14 or Magoh, while Magoh and Y14 associate with each other, but not with eIF4AIII, CWC22 or the nucleolar proteins. Our data argue against the presence of a functional EJC in trypanosomes, but rather indicate that eIF4AIII adopted non-EJC related, essential functions, while Magoh and Y14 became redundant. Trypanosomes also possess homologues to the NMD proteins UPF1 and UPF2. We found that depletion of UPF1 causes only a minor reduction in growth and detailed phylogenetic analyses show several independent losses of UPF1 and UPF2, as well as total loss of UPF3 in the Kinetoplastida group. The data indicate that UPF1-dependent NMD is not essential in trypanosomes consistent with the observation that the cells tolerate the presence of mRNAs with allele-specific, endogenous PTCs (premature termination codons). Altogether, our comprehensive analyses of conserved components provide no evidence for a canonical EJC or NMD pathway in (almost) intron-less trypanosomatids.

show abstract

Section: Resultsmentioning

confidence: 99%

Intron-loss in Kinetoplastea correlates with a non-functional EJC and loss of NMD factors

Gabiatti,

Freire,

Odenwald

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…pombe in which degradation of PTC-containing mRNA is not affected by the deletion of MAGO 52,53 . Recent publications now report that the EJC is not linked to NMD in other unicellular eukaryotes 54,55 .…”

Section: Discussionmentioning

confidence: 99%

Exon junction complex components Y14 and Mago still play a role in budding yeast

Boisramé

Devillers

Onésime

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Since their divergence from Pezizomycotina, the mRNA metabolism of budding yeasts have undergone regressive evolution. With the dramatic loss of introns, a number of quality control mechanisms have been simplified or lost during evolution, such as the exon junction complex (EJC). We report the identification of the core EJC components, Mago, Y14, and eIF4A3, in at least seven Saccharomycotina species, including Yarrowia lipolytica. Peripheral factors that join EJC, either to mediate its assembly (Ibp160 or Cwc22), or trigger downstream processes, are present in the same species, forming an evolutionary package. Co-immunoprecipitation studies in Y. lipolytica showed that Mago and Y14 have retained the capacity to form heterodimers, which successively bind to the peripheral factors Upf3, Aly/REF, and Pym. Phenotypes and RNA-Seq analysis of EJC mutants showed evidence of Y14 and Mago involvement in mRNA metabolism. Differences in unspliced mRNA levels suggest that Y14 binding either interferes with pre-mRNA splicing or retains mRNA in the nucleus before their export and translation. These findings indicate that yeast could be a relevant model for understanding EJC function.

show abstract

“…Moreover, EJC binds to strong splicing sites, CG-rich hexamers [ 77 ]. In addition to large introns, EJC can also regulate the splicing of many mini-introns in P. tetraurelia , suggesting that a fine-tuning expression of EJC genes is required for steady intron removal [ 78 ].…”

Section: The Ejc Plays a Crucial Role In Neurodevelopmental Disordersmentioning

confidence: 99%

Diverse Roles of the Exon Junction Complex Factors in the Cell Cycle, Cancer, and Neurodevelopmental Disorders-Potential for Therapeutic Targeting

Martin

Rupkey

Asthana

et al. 2022

IJMS

View full text Add to dashboard Cite

The exon junction complex (EJC) plays a crucial role in regulating gene expression at the levels of alternative splicing, translation, mRNA localization, and nonsense-mediated decay (NMD). The EJC is comprised of three core proteins: RNA-binding motif 8A (RBM8A), Mago homolog (MAGOH), eukaryotic initiation factor 4A3 (eIF4A3), and a peripheral EJC factor, metastatic lymph node 51 (MLN51), in addition to other peripheral factors whose structural integration is activity-dependent. The physiological and mechanistic roles of the EJC in contribution to molecular, cellular, and organismal level function continue to be explored for potential insights into genetic or pathological dysfunction. The EJC’s specific role in the cell cycle and its implications in cancer and neurodevelopmental disorders prompt enhanced investigation of the EJC as a potential target for these diseases. In this review, we highlight the current understanding of the EJC’s position in the cell cycle, its relation to cancer and developmental diseases, and potential avenues for therapeutic targeting.

show abstract

The splicing of tiny introns of Paramecium is controlled by MAGO

Cited by 3 publications

References 21 publications

Intron-loss in Kinetoplastea correlates with a non-functional EJC and loss of NMD factors

Intron-loss in Kinetoplastea correlates with a non-functional EJC and loss of NMD factors

Exon junction complex components Y14 and Mago still play a role in budding yeast

Diverse Roles of the Exon Junction Complex Factors in the Cell Cycle, Cancer, and Neurodevelopmental Disorders-Potential for Therapeutic Targeting

Contact Info

Product

Resources

About