From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory

Andjus, Sara; Morillon, Antonin; Wéry, Maxime

doi:10.3390/ncrna7030044

Cited by 22 publications

(16 citation statements)

References 179 publications

(239 reference statements)

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“…Furthermore, in our data there are 60 interactions involving 83 proteins encoded by LINC genes (long intergenic non-protein coding RNA), 67 of which are annotated as “uncertain”. A fraction of this dataset is expected to be updated into fully characterized LINC-encoded microproteins [ 44 ]. In the most recent protein evidence update of NeXtProt [ 20 ], 1, 12 and 8 of the 83 uncertain protein products of LINC genes were, respectively, upgraded to PE1, PE2 and PE4 levels.…”

Section: Discussionmentioning

confidence: 99%

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

2022

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After more than fifteen years from the first high-throughput experiments for human protein–protein interaction (PPI) detection, we are still wondering how close the completion of the genome-scale human PPI network reconstruction is, what needs to be further explored and whether the biological insights gained from the holistic investigation of the current network are valid and useful. The unique structure of PICKLE, a meta-database of the human experimentally determined direct PPI network developed by our group, presently covering ~80% of the UniProtKB/Swiss-Prot reviewed human complete proteome, enables the evaluation of the interactome expansion by comparing the successive PICKLE releases since 2013. We observe a gradual overall increase of 39%, 182%, and 67% in protein nodes, PPIs, and supporting references, respectively. Our results indicate that, in recent years, (a) the PPI addition rate has decreased, (b) the new PPIs are largely determined by high-throughput experiments and mainly concern existing protein nodes and (c), as we had predicted earlier, most of the newly added protein nodes have a low degree. These observations, combined with a largely overlapping k-core between PICKLE releases and a network density increase, imply that an almost complete picture of a structurally defined network has been reached. The comparative unsupervised application of two clustering algorithms indicated that exploring the full interactome topology can reveal the protein neighborhoods involved in closely related biological processes as transcriptional regulation, cell signaling and multiprotein complexes such as the connexon complex associated with cancers. A well-reconstructed human protein interactome is a powerful tool in network biology and medicine research forming the basis for multi-omic and dynamic analyses.

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Section: Discussionmentioning

confidence: 99%

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

2022

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“…NMD is a well-conserved cytoplasmic mRNA quality control mechanism that has been found in species across the eukaryotic kingdom [45,46]. Although it was originally discovered to target PTC-containing transcripts, later research revealed that a large portion of normal, error-free mRNAs and some non-coding RNA species are also substrates of this pathway (reviewed in [56]). Thus, NMD functions beyond quality control and is now considered as a more general mechanism for post-transcriptional gene regulation [57,58].…”

Section: Further Surveillance In the Cytoplasm-detection Of Errors Via Nonsense-mediated Decaymentioning

confidence: 99%

“…In addition, transcriptome-wide analysis of yeast RNPs has revealed that Gbp2 is also strongly associated with small nucleolar RNAs and long noncoding (lnc) RNAs [117]. Subsequent reports demonstrated that lncRNAs engaged in translation could be targeted to NMD, and this is functionally significant for the regulation of gene expression [56,68,150,151]. Recent reports have further implicated a regulatory interplay between human SR proteins, microRNAs, and lncRNAs underlying oncogenic or other health effects [152][153][154][155][156].…”

Section: Closing Remarksmentioning

confidence: 99%

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

Krebber

2021

IJMS

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Pre-mRNA splicing is critical for cells, as defects in this process can lead to altered open reading frames and defective proteins, potentially causing neurodegenerative diseases and cancer. Introns are removed in the nucleus and splicing is documented by the addition of exon-junction-complexes (EJCs) at exon-exon boundaries. This “memory” of splicing events is important for the ribosome, which translates the RNAs in the cytoplasm. In case a stop codon was detected before an EJC, translation is blocked and the RNA is eliminated by the nonsense-mediated decay (NMD). In the model organism Saccharomyces cerevisiae, two guard proteins, Gbp2 and Hrb1, have been identified as nuclear quality control factors for splicing. In their absence, intron-containing mRNAs leak into the cytoplasm. Their presence retains transcripts until the process is completed and they release the mRNAs by recruitment of the export factor Mex67. On transcripts that experience splicing problems, these guard proteins recruit the nuclear RNA degradation machinery. Interestingly, they continue their quality control function on exported transcripts. They support NMD by inhibiting translation and recruiting the cytoplasmic degradation factors. In this way, they link the nuclear and cytoplasmic quality control systems. These discoveries are also intriguing for humans, as homologues of these guard proteins are present also in multicellular organisms. Here, we provide an overview of the quality control mechanisms of pre-mRNA splicing, and present Gbp2 and Hrb1, as well as their human counterparts, as important players in these pathways.

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“…They make an intimate part of mechanisms controlling cell/tissue homeostasis as well as various diseases including cancers (Rinn & Chang, 2012) now nicely reported in the CLC2 lncRNA database (Vancura et al., 2021). Although lncRNAs were initially defined as noncoding, several contain open reading frames (ORFs) that are translated into functional peptides and subjected to translation‐dependent decay (Andjus et al., 2021; Chen, 2020). Among lncRNAs, circRNAs are circular molecules with a covalently closed loop structure lacking 5′cap and 3′polyadenylated tail, formed through noncanonical splicing (Kristensen et al., 2019).…”

Section: Introductionmentioning

confidence: 99%

Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer

Almeida

Gabriel

Firlej

et al. 2022

J of Extracellular Vesicle

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Long noncoding (lnc)RNAs modulate gene expression alongside presenting unexpected source of neoantigens. Despite their immense interest, their ability to be transferred and control adjacent cells is unknown. Extracellular Vesicles (EVs) offer a protective environment for nucleic acids, with pro and antitumourigenic functions by controlling the immune response. In contrast to extracellular nonvesicular RNA, few studies have addressed the full RNA content within human fluids' EVs and have compared them with their tissue of origin. Here, we performed Total RNA-Sequencing on six Formalin-Fixed-Paraffin-Embedded (FFPE) prostate cancer (PCa) tumour tissues and their paired urinary (u)EVs to provide the first whole transcriptome comparison from the same patients. UEVs contain simplified transcriptome with intronfree cytoplasmic transcripts and enriched lnc/circular (circ)RNAs, strikingly common to an independent 20 patients' urinary cohort. Our full cellular and EVs transcriptome comparison within three PCa cell lines identified a set of overlapping 14 uEV-circRNAs characterized as essential for prostate cell proliferation in vitro and 28 uEV-lncRNAs belonging to the cancer-related lncRNA census (CLC2). In addition, we found 15 uEV-lncRNAs, predicted to encode 768 high-affinity neoantigens, and for which three of the encoded-ORF produced detectable unmodified peptidesThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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From Yeast to Mammals, the Nonsense-Mediated mRNA Decay as a Master Regulator of Long Non-Coding RNAs Functional Trajectory

Cited by 22 publications

References 179 publications

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

Nuclear mRNA Quality Control and Cytoplasmic NMD Are Linked by the Guard Proteins Gbp2 and Hrb1

Urinary extracellular vesicles contain mature transcriptome enriched in circular and long noncoding RNAs with functional significance in prostate cancer

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