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Smith and Bartel show that mRNA recruitment to stress granules imparts resistance to the integrated stress response translational shutdown.

MiR-34 is a tumour suppressor microRNA known to be upregulated by p53 after DNA damage and plays a critical role in cell cycle arrest and apoptosis. Here the authors show the cell maintains an inactive pool of miR-34 which is rapidly activated after damage via ATM-dependent phosphorylation.

MicroRNAs are known to affect the levels of both messenger RNA (mRNA) and protein. But as protein production is dependent on the presence of mRNA, it was not clear what the relative contributions of microRNA-mediated mRNA cleavage and translational repression were. These authors have parsed out the two mechanisms, and unexpectedly find that microRNAs function primarily by affecting mRNA levels rather than their translation. This suggests a reassessment of many previous conclusions is necessary.

In vivo existence of guanine-rich four-stranded RNA structures (G4-RNAs) has been a matter of debate. Here the authors developed a protocol, G4RP-seq, to capture and identify transcriptome-wide G4-RNA, providing insights into the formation of transient G4-RNA in live human cells.

In one of two studies, a technique known as SILAC is used to measure, on a large scale, changes in protein level as a function of expression of endogenous and exogenous miRNAs. It is found that although miRNAs directly repress the translation of hundreds of genes, additional indirect effects result in changes in expression of thousands of genes.

Klebsiella pneumoniae is an opportunistic pathogen of increasing public health concern due to the prevalence of antimicrobial resistance. Here, the authors provide insight into the resistance profiles, bacterial genome features and virulence genes, in a year-long prospective study of K. pneumoniae clinical isolates.

A new high-throughput sequencing method to determine mRNA poly(A)-tail length enabled studies of individual RNAs across species and developmental stages to investigate the role of poly(A) length in translational regulation; the relationship between poly(A) length and translational efficiency shown in early embryo systems does not occur later in development, a finding that explains different regulatory consequences of microRNAs acting at different developmental times.

Gene regulation in oocytes relies heavily on poly(A) tail-length changes. Here, the authors develop PAL-AI, a neural network model that predicts tail-length changes, identifies regulatory motifs, and links disruptive genetic variants to negative selection in humans, implicating tail-length control in female fertility.

Mutation of Cid14, a key enzyme in the TRAMP RNA surveillance pathway, has previously been shown to decrease small interfering RNA production in Schizosaccharomyces pombe. Analysis of Argonaute-associated proteins now indicates that, in the absence of Cid14, RNAs usually processed by TRAMP now enter the small interfering RNA pathway, suggesting that the RNA surveillance pathway prevents abundant RNAs from entering the RNA interference pathway.

Transcriptome sequencing and analysis of hybrid embryos show that in contrast to early animal embryogenesis, early plant embryogenesis is mostly under zygotic control.

Despite a rise in COVID-19 cases among children, there is limited understanding of the antibody responses mounted, compared to in adults. In this work, authors compare seroconversion rates and antibody responses in unvaccinated Australian children across the three SARS-CoV-2 waves (Wuhan, Delta and Omicron).

The discovery that mRNA degradation and deadenylation are uncoupled during meiosis in budding yeast provides a unique context to examine the regulation of each process individually, and reveals that transcript length is a determinant of deadenylation rates across eukaryotes.

Transcriptome-wide profiling studies in mammalian cells show that the stringency of start-codon selection is increased during mitosis, and that this is regulated by nuclear eIF1 to preserve mitotic arrest physiology.

In the RNA world, there would have been ribozymes able to catalyze RNA replication. An artificial ribozyme able to catalyze RNA-templated RNA polymerization has been developed. Now biochemical work and crystal structures of this ribozyme's catalytic core trapped in a state prior to catalysis reveal the complex catalytic strategies it employs.

In addition to their function in gene regulation, certain microRNAs can be secreted by cells. Here, the authors show that the microRNA let-7 can cause neurodegeneration by directly activating Toll-like receptor 7 and that individuals with Alzheimer's disease have more let-7b in their cerebrospinal fluid.

The genomic sequences of 12 Drosophila species for conserved elements and describe the relationship between conservation and function for many specific sequence motifs.

When genes are transcribed into RNA, the polymerase extends beyond the end of the protein-coding portion to make the 3′ untranslated region (UTR); this region contains important regulatory sequences, such as microRNA binding sites, and facilitates translation. Long tracts of untemplated adenines are added to the 3′ UTR, and the standard method for sequencing the transcriptome is based on hybridization to the poly(A) tail. A new high-throughput approach to transcriptome sequencing is reported that avoids a known limitation of the poly(A) method; the method is used to provide a more accurate analysis of functional and evolutionary aspects of 3′ UTRs of the nematode.

Argonaute proteins are an essential part of the guide-RNA–protein complex that carries out RNA-induced gene silencing; structure–function studies of the yeast complex reveal conserved features of the eukaryotic complex, which underlie formation of the catalytically active conformation.

Single-nucleotide polymorphisms in microRNA target sites can disrupt the effects of the microRNA. Kim and Bartel use sequencing to investigate this phenomenon on a large scale and find that such polymorphisms generate gene-regulatory diversity in mice.

Ime4p is a yeast N6-methyladenosine (m6A) methyltransferase with an unknown role in meiosis. Rme1p is a repressor of meiosis. Here the authors show that Ime4p methylates RME1 3′ UTR to reduce its expression and enable meiosis, thus providing an example of an m6A site with a physiological role.

A set of 34 excised introns in Saccharomyces cerevisiae, characterized by having a short distance between the lariat branch point and the 3′ splice site, have a biological function within the TOR growth-signalling network.

The structure of the RuvA tetramer suggests how Holliday junctions are maintained in a conformation that facilitates branch migration during recombination.

A single miRNA can target hundreds of distinct transcripts, but some miRNAs such as C. elegans lsy-6 have very low target proficiency. The reasons behind this are now identified as weak seed-pairing stability and high target-site abundance. These findings have implications for understanding off-target effects of siRNAs and improving miRNA target predictions.

An autonomous laboratory, the A-Lab, is presented that combines computations, literature data, machine learning and active learning, which discovered and synthesized 41 novel compounds from a set of 58 targets after 17 days of operation.

This paper shows that the Drosophila genome encodes endogenous siRNAs. Derived from long hairpin RNA genes, these siRNAs downregulate protein expression. Their processing pathway from the hairpin into the mature ∼21-nucleotide siRNA involves factors of two pathways thought to be distinct.

MicroRNAs (miRNAs) are produced through a set of cleavages within a longer RNA, one of the nucleases involved in this process is Drosha. A subset of miRNAs (mirtrons) are matured through an alternative pathway that is Drosha-independent. These mirtrons may be the early ancestors of the majority of miRNAs that were expressed once Drosha function emerged.

Decline of the Tasmanian devil due to transmissible cancer has allowed mesopredator release of the spotted-tailed quoll. Population genomic analysis of the quoll shows the effect of devil decline on population structure, and selection on genes, including those for muscle development and locomotion.

The crystal structure of the fructose-2,6-bisphosphatase domain trapped during the reaction reveal a phosphorylated His 258, and a water molecule immobilized by the product, fructose-6-phosphate. The geometry suggests that the dephosphorylation step requires prior removal of the product for an ‘associative in-line’ phosphoryl transfer to the catalytic water.

A molecular tweezer has been shown to bind to the surface of a 14-3-3 protein through a particular lysine residue. This interaction — characterized in detail by protein crystallography and computational modelling — disrupts the protein's binding with partner proteins. These findings ascertain supramolecular chemistry as an enticing tool in chemical biology, here towards modulating protein functions.

Hox clusters, which confer axial patterning on bilaterian embryos, also contain microRNAs. This analysis suggests that these microRNAs specifically target the Hox genes that lie to their 3′ side, thereby reinforcing the dominance of posterior Hox genes over anterior ones.