Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods.

RNA editing, a post-transcriptional process, allows the diversification of proteomes beyond the genomic blueprint; however it is infrequently used among animals for this purpose. Recent reports suggesting increased levels of RNA editing in squids thus raise the question of the nature and effects of these events. We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites. Editing is enriched in the nervous system, affecting molecules pertinent for excitability and neuronal morphology. The genomic sequence flanking editing sites is highly conserved, suggesting that the process confers a selective advantage. Due to the large number of sites, the surrounding conservation greatly reduces the number of mutations and genomic polymorphisms in protein-coding regions. This trade-off between genome evolution and transcriptome plasticity highlights the importance of RNA recoding as a strategy for diversifying proteins, particularly those associated with neural function. PAPERCLIP.

Alternative Splicing Variation: Accessing and Exploiting in Crop Improvement Programs.

Alternative splicing (AS) is a gene regulatory mechanism modulating gene expression in multiple ways. AS is prevalent in all eukaryotes including plants. AS generates two or more mRNAs from the precursor mRNA (pre-mRNA) to regulate transcriptome complexity and proteome diversity. Advances in next-generation sequencing, omics technology, bioinformatics tools, and computational methods provide new opportunities to quantify and visualize AS-based quantitative trait variation associated with plant growth, development, reproduction, and stress tolerance. Domestication, polyploidization, and environmental perturbation may evolve novel splicing variants associated with agronomically beneficial traits. To date, pre-mRNAs from many genes are spliced into multiple transcripts that cause phenotypic variation for complex traits, both in model plant Arabidopsis and field crops. Cataloguing and exploiting such variation may provide new paths to enhance climate resilience, resource-use efficiency, productivity, and nutritional quality of staple food crops. This review provides insights into AS variation alongside a gene expression analysis to select for novel phenotypic diversity for use in breeding programs. AS contributes to heterosis, enhances plant symbiosis (mycorrhiza and rhizobium), and provides a mechanistic link between the core clock genes and diverse environmental clues.

Nuclear and mitochondrial RNA editing systems have opposite effects on protein diversity.

RNA editing can yield protein products that differ from those directly encoded by genomic DNA. This process is pervasive in the mitochondria of many eukaryotes, where it predominantly results in the restoration of ancestral protein sequences. Nuclear mRNAs in metazoans also undergo editing (adenosine-to-inosine or 'A-to-I' substitutions), and most of these edits appear to be nonadaptive 'misfirings' of adenosine deaminases. However, recent analysis of cephalopod transcriptomes found that many editing sites are shared by anciently divergent lineages within this group, suggesting they play some adaptive role. Recent discoveries have also revealed that some fungi have an independently evolved A-to-I editing mechanism, resulting in extensive recoding of their nuclear mRNAs. Here, phylogenetic comparisons were used to determine whether RNA editing generally restores ancestral protein sequences or creates derived variants. Unlike in mitochondrial systems, RNA editing in metazoan and fungal nuclear transcripts overwhelmingly leads to novel sequences not found in inferred ancestral proteins. Even for the subset of RNA editing sites shared by deeply divergent cephalopod lineages, the primary effect of nuclear editing is an increase-not a decrease-in protein divergence. These findings suggest fundamental differences in the forces responsible for the evolution of RNA editing in nuclear versus mitochondrial systems.

Is the cellular initiation of translation an exclusive property of the initiator tRNAs?

Translation of mRNAs is the primary function of the ribosomal machinery. Although cells allow for a certain level of translational errors/mistranslation (which may well be a strategic need), maintenance of the fidelity of translation is vital for the cellular function and fitness. The P-site bound initiator tRNA selects the start codon in an mRNA and specifies the reading frame. A direct P-site binding of the initiator tRNA is a function of its special structural features, ribosomal elements, and the initiation factors. A highly conserved feature of the 3 consecutive G:C base pairs (3 GC pairs) in the anticodon stem of the initiator tRNAs is vital in directing it to the P-site. Mutations in the 3 GC pairs diminish/abolish initiation under normal physiological conditions. Using molecular genetics approaches, we have identified conditions that allow initiation with the mutant tRNAs in Escherichia coli. During our studies, we have uncovered a novel phenomenon of in vivo initiation by elongator tRNAs. Here, we recapitulate how the cellular abundance of the initiator tRNA, and nucleoside modifications in rRNA are connected with the tRNA selection in the P-site. We then discuss our recent finding of how a conserved feature in the mRNA, the Shine-Dalgarno sequence, influences tRNA selection in the P-site.

Post-translational modifications and their implications in cancer.

Post-translational modifications (PTMs) are crucial regulatory mechanisms that alter the properties of a protein by covalently attaching a modified chemical group to some of its amino acid residues. PTMs modulate essential physiological processes such as signal transduction, metabolism, protein localization, and turnover and have clinical relevance in cancer and age-related pathologies. Majority of proteins undergo post-translational modifications, irrespective of their occurrence in or after protein biosynthesis. Post-translational modifications link to amino acid termini or side chains, causing the protein backbone to get cleaved, spliced, or cyclized, to name a few. These chemical modifications expand the diversity of the proteome and regulate protein activity, structure, locations, functions, and protein-protein interactions (PPIs). This ability to modify the physical and chemical properties and functions of proteins render PTMs vital. To date, over 200 different protein modifications have been reported, owing to advanced detection technologies. Some of these modifications include phosphorylation, glycosylation, methylation, acetylation, and ubiquitination. Here, we discuss about the existing as well as some novel post-translational protein modifications, with their implications in aberrant states, which will help us better understand the modified sites in different proteins and the effect of PTMs on protein functions in core biological processes and progression in cancer.

Alternative splicing: An efficient regulatory approach towards plant developmental plasticity.

Alternative splicing (AS) is a gene regulatory mechanism that plants adapt to modulate gene expression (GE) in multiple ways. AS generates alternative isoforms of the same gene following various development and environmental stimuli, increasing transcriptome plasticity and proteome complexity. AS controls the expression levels of certain genes and regulates GE networks that shape plant adaptations through nonsense-mediated decay (NMD). This review intends to discuss AS modulation, from interaction with noncoding RNAs to the established roles of splicing factors (SFs) in response to endogenous and exogenous cues. We aim to gather such studies that highlight the magnitude and impact of AS, which are not always clear from individual articles, when AS is increasing in individual genes and at a global level. This work also anticipates making plant researchers know that AS is likely to occur in their investigations and that dynamic changes in AS and their effects must be frequently considered. We also review our understanding of AS-mediated posttranscriptional modulation of plant stress tolerance and discuss its potential application in crop improvement in the future. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Processing > Splicing Mechanisms RNA-Based Catalysis > RNA Catalysis in Splicing and Translation.

Mouse Organ-Specific Proteins and Functions.

Organ-specific proteins (OSPs) possess great medical potential both in clinics and in biomedical research. Applications of them-such as alanine transaminase, aspartate transaminase, and troponins-in clinics have raised certain concerns of their organ specificity. The dynamics and diversity of protein expression in heterogeneous human populations are well known, yet their effects on OSPs are less addressed. Here, we used mice as a model and implemented a breadth study to examine the panorgan proteome for potential variations in organ specificity in different genetic backgrounds. Using reasonable resources, we generated panorgan proteomes of four in-bred mouse strains. The results revealed a large diversity that was more profound among OSPs than among proteomes overall. We defined a robustness score to quantify such variation and derived three sets of OSPs with different stringencies. In the meantime, we found that the enriched biological functions of OSPs are also organ-specific and are sensitive and useful to assess the quality of OSPs. We hope our breadth study can open doors to explore the molecular diversity and dynamics of organ specificity at the protein level.

Comprehensive analysis of mutually exclusive alternative splicing in C. elegans.

Mutually exclusive selection of one exon in a cluster of exons is a rare form of alternative pre-mRNA splicing, yet suggests strict regulation. However, the repertoires of regulation mechanisms for the mutually exclusive (ME) splicing in vivo are still unknown. Here, we experimentally explore putative ME exons in C. elegans to demonstrate that 29 ME exon clusters in 27 genes are actually selected in a mutually exclusive manner. Twenty-two of the clusters consist of homologous ME exons. Five clusters have too short intervening introns to be excised between the ME exons. Fidelity of ME splicing relies at least in part on nonsense-mediated mRNA decay for 14 clusters. These results thus characterize all the repertoires of ME splicing in this organism.