m6A mRNA Destiny: Chained to the rhYTHm by the YTH-Containing Proteins

The control of gene expression is a multi-layered process occurring at the level of DNA, RNA, and proteins. With the emergence of highly sensitive techniques, new aspects of RNA regulation have been uncovered leading to the emerging field of epitranscriptomics dealing with RNA modifications. Among those post-transcriptional modifications, N6-methyladenosine (m6A) is the most prevalent in messenger RNAs (mRNAs). This mark can either prevent or stimulate the formation of RNA-protein complexes, thereby influencing mRNA-related mechanisms and cellular processes. This review focuses on proteins containing a YTH domain (for YT521-B Homology), a small building block, that selectively detects the m6A nucleotide embedded within a consensus motif. Thereby, it contributes to the recruitment of various effectors involved in the control of mRNA fates through adjacent regions present in the different YTH-containing proteins.

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Distinct RNA-unwinding mechanisms of DEAD-box and DEAH-box RNA helicase proteins in remodeling structured RNAs and RNPs

Biochemical Society Transactions ◽

10.1042/bst20170095 ◽

2017 ◽

Vol 45 (6) ◽

pp. 1313-1321 ◽

Cited By ~ 27

Author(s):

Benjamin Gilman ◽

Pilar Tijerina ◽

Rick Russell

Keyword(s):

Conformational Changes ◽

Protein Complexes ◽

Rna Helicase ◽

Conformational Transitions ◽

Messenger Rnas ◽

Base Pairs ◽

Dead Box ◽

Evolutionarily Conserved ◽

Partially Unfolded ◽

Rna Protein Complexes

Structured RNAs and RNA–protein complexes (RNPs) fold through complex pathways that are replete with misfolded traps, and many RNAs and RNPs undergo extensive conformational changes during their functional cycles. These folding steps and conformational transitions are frequently promoted by RNA chaperone proteins, notably by superfamily 2 (SF2) RNA helicase proteins. The two largest families of SF2 helicases, DEAD-box and DEAH-box proteins, share evolutionarily conserved helicase cores, but unwind RNA helices through distinct mechanisms. Recent studies have advanced our understanding of how their distinct mechanisms enable DEAD-box proteins to disrupt RNA base pairs on the surfaces of structured RNAs and RNPs, while some DEAH-box proteins are adept at disrupting base pairs in the interior of RNPs. Proteins from these families use these mechanisms to chaperone folding and promote rearrangements of structured RNAs and RNPs, including the spliceosome, and may use related mechanisms to maintain cellular messenger RNAs in unfolded or partially unfolded conformations.

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Spliceosomal snRNA Epitranscriptomics

Frontiers in Genetics ◽

10.3389/fgene.2021.652129 ◽

2021 ◽

Vol 12 ◽

Author(s):

Pedro Morais ◽

Hironori Adachi ◽

Yi-Tao Yu

Keyword(s):

Cell Nucleus ◽

Current Knowledge ◽

Protein Complexes ◽

Mrna Splicing ◽

Rna Modifications ◽

Small Nuclear Rnas ◽

Sequence Elements ◽

Critical Components ◽

Rna Protein Complexes ◽

Small Nuclear Ribonucleoproteins

Small nuclear RNAs (snRNAs) are critical components of the spliceosome that catalyze the splicing of pre-mRNA. snRNAs are each complexed with many proteins to form RNA-protein complexes, termed as small nuclear ribonucleoproteins (snRNPs), in the cell nucleus. snRNPs participate in pre-mRNA splicing by recognizing the critical sequence elements present in the introns, thereby forming active spliceosomes. The recognition is achieved primarily by base-pairing interactions (or nucleotide-nucleotide contact) between snRNAs and pre-mRNA. Notably, snRNAs are extensively modified with different RNA modifications, which confer unique properties to the RNAs. Here, we review the current knowledge of the mechanisms and functions of snRNA modifications and their biological relevance in the splicing process.

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E3 ubiquitin ligases

Essays in Biochemistry ◽

10.1042/bse0410015 ◽

2005 ◽

Vol 41 ◽

pp. 15-30 ◽

Cited By ~ 123

Author(s):

Helen C. Ardley ◽

Philip A. Robinson

Keyword(s):

Protein Complexes ◽

Loss Of Function ◽

Direct Role ◽

Cellular Processes ◽

Substrate Protein ◽

Protein Ubiquitination ◽

C Terminus ◽

Full Complement ◽

Spatio Temporal ◽

Eukaryotic Organisms

The selectivity of the ubiquitin–26 S proteasome system (UPS) for a particular substrate protein relies on the interaction between a ubiquitin-conjugating enzyme (E2, of which a cell contains relatively few) and a ubiquitin–protein ligase (E3, of which there are possibly hundreds). Post-translational modifications of the protein substrate, such as phosphorylation or hydroxylation, are often required prior to its selection. In this way, the precise spatio-temporal targeting and degradation of a given substrate can be achieved. The E3s are a large, diverse group of proteins, characterized by one of several defining motifs. These include a HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene) or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Whereas HECT E3s have a direct role in catalysis during ubiquitination, RING and U-box E3s facilitate protein ubiquitination. These latter two E3 types act as adaptor-like molecules. They bring an E2 and a substrate into sufficiently close proximity to promote the substrate's ubiquitination. Although many RING-type E3s, such as MDM2 (murine double minute clone 2 oncoprotein) and c-Cbl, can apparently act alone, others are found as components of much larger multi-protein complexes, such as the anaphase-promoting complex. Taken together, these multifaceted properties and interactions enable E3s to provide a powerful, and specific, mechanism for protein clearance within all cells of eukaryotic organisms. The importance of E3s is highlighted by the number of normal cellular processes they regulate, and the number of diseases associated with their loss of function or inappropriate targeting.

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Current RNA-based Therapeutics in Clinical Trials

Current Gene Therapy ◽

10.2174/1566523219666190719100526 ◽

2019 ◽

Vol 19 (3) ◽

pp. 172-196 ◽

Cited By ~ 15

Author(s):

Ling-Yan Zhou ◽

Zhou Qin ◽

Yang-Hui Zhu ◽

Zhi-Yao He ◽

Ting Xu

Keyword(s):

Clinical Trials ◽

Rapid Development ◽

Genetic Diseases ◽

Three Dimensional ◽

Therapeutic Effects ◽

Messenger Rnas ◽

Small Interfering Rnas ◽

Rna Modifications ◽

Guide Rna ◽

Endogenous Genes

Long-term research on various types of RNAs has led to further understanding of diverse mechanisms, which eventually resulted in the rapid development of RNA-based therapeutics as powerful tools in clinical disease treatment. Some of the developing RNA drugs obey the antisense mechanisms including antisense oligonucleotides, small interfering RNAs, microRNAs, small activating RNAs, and ribozymes. These types of RNAs could be utilized to inhibit/activate gene expression or change splicing to provide functional proteins. In the meantime, some others based on different mechanisms like modified messenger RNAs could replace the dysfunctional endogenous genes to manage some genetic diseases, and aptamers with special three-dimensional structures could bind to specific targets in a high-affinity manner. In addition, the recent most popular CRISPR-Cas technology, consisting of a crucial single guide RNA, could edit DNA directly to generate therapeutic effects. The desired results from recent clinical trials indicated the great potential of RNA-based drugs in the treatment of various diseases, but further studies on improving delivery materials and RNA modifications are required for the novel RNA-based drugs to translate to the clinic. This review focused on the advances and clinical studies of current RNA-based therapeutics, analyzed their challenges and prospects.

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Alu RNA-protein complexes formed in vitro react with a novel lupus autoantibody.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)39098-1 ◽

1985 ◽

Vol 260 (21) ◽

pp. 11781-11786

Author(s):

R Kole ◽

L D Fresco ◽

J D Keene ◽

P L Cohen ◽

R A Eisenberg ◽

...

Keyword(s):

Protein Complexes ◽

Alu Rna ◽

Rna Protein Complexes

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Arabidopsis thaliana G3BP Ortholog Rescues Mammalian Stress Granule Phenotype across Kingdoms

International Journal of Molecular Sciences ◽

10.3390/ijms22126287 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6287

Author(s):

Hendrik Reuper ◽

Benjamin Götte ◽

Lucy Williams ◽

Timothy J. C. Tan ◽

Gerald M. McInerney ◽

...

Keyword(s):

Arabidopsis Thaliana ◽

Fusion Proteins ◽

Biological Function ◽

Protein Complexes ◽

Protein Family ◽

Knock Out ◽

Marker Proteins ◽

Interaction Partners ◽

Functional Analyses ◽

Rna Protein Complexes

Stress granules (SGs) are dynamic RNA–protein complexes localized in the cytoplasm that rapidly form under stress conditions and disperse when normal conditions are restored. The formation of SGs depends on the Ras-GAP SH3 domain-binding protein (G3BP). Formations, interactions and functions of plant and human SGs are strikingly similar, suggesting a conserved mechanism. However, functional analyses of plant G3BPs are missing. Thus, members of the Arabidopsis thaliana G3BP (AtG3BP) protein family were investigated in a complementation assay in a human G3BP knock-out cell line. It was shown that two out of seven AtG3BPs were able to complement the function of their human homolog. GFP-AtG3BP fusion proteins co-localized with human SG marker proteins Caprin-1 and eIF4G1 and restored SG formation in G3BP double KO cells. Interaction between AtG3BP-1 and -7 and known human G3BP interaction partners such as Caprin-1 and USP10 was also demonstrated by co-immunoprecipitation. In addition, an RG/RGG domain exchange from Arabidopsis G3BP into the human G3BP background showed the ability for complementation. In summary, our results support a conserved mechanism of SG function over the kingdoms, which will help to further elucidate the biological function of the Arabidopsis G3BP protein family.

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Interphotoreceptor coupling: an evolutionary perspective

Pflügers Archiv - European Journal of Physiology ◽

10.1007/s00424-021-02572-9 ◽

2021 ◽

Author(s):

Lorenzo Cangiano ◽

Sabrina Asteriti

Keyword(s):

Visual Information ◽

Signal To Noise Ratio ◽

Electrical Coupling ◽

Physiological Role ◽

Cellular Processes ◽

Contact Points ◽

Highly Sensitive ◽

The Many ◽

The Impact

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.

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