MicroRNAs (miRNAs) are short (∼22 nt) non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.

Transfer RNAs (tRNAs) are key players of protein synthesis, as they decode the genetic information organized in mRNA codons, translating them into the code of 20 amino acids. To be fully active, tRNAs undergo extensive post-transcriptional modifications, catalyzed by different tRNA-modifying enzymes. Lack of these modifications increases the level of missense errors and affects codon decoding rate, contributing to protein aggregation with deleterious consequences to the cell. Recent works show that tRNA hypomodification and tRNA-modifying-enzyme deregulation occur in several diseases where proteostasis is affected, namely, neurodegenerative and metabolic diseases. In this review, we discuss the recent findings that correlate aberrant tRNA modification with proteostasis imbalances, in particular in neurological and metabolic disorders, and highlight the association between tRNAs, their modifying enzymes, translational decoding, and disease onset.

Until recently, transfer RNAs (tRNAs) were thought to function in protein translation only. However, recent findings demonstrate that both pre- and mature tRNAs can undergo endonucleolytic cleavage by different ribonucleases originating different types of small non-coding RNAs, known as tRNA-derived fragments (tRFs). tRFs are classified according to their origin and are implicated in various cellular processes, namely apoptosis, protein synthesis control, and RNA interference. Although their functions are still poorly understood, their mechanisms of action vary according to the tRF sub-type. Several tRFs have been associated with cancer, neurodegenerative disorders, and viral infections and growing evidence shows that they may constitute novel molecular targets for modulating pathological processes. Here, we recapitulate the current knowledge of tRF biology, highlight the known functions and mechanisms of action of the different sub-classes of tRFs and discuss their implications in human disease. WIREs RNA 2017, 8:e1423. doi: 10.1002/wrna.1423 For further resources related to this article, please visit the WIREs website.

The extant biosynthesis of tetrapyrrole macrocycles has been considered a paradigm for the prebiotic formation of such molecules, yet only a few analogous non-enzymic reactions along the overall process have been demonstrated. In a prior study, the aqueous non-enzymic reaction of a dione and an aminoketone (d-aminolevulinic acid) afforded uroporphyrinogen, Nature's last universal precursor to all extant tetrapyrroles. Here, in one flask the non-enzymic combinatorial reaction of two diones (substituents = acetic acid and methyl) and two aminoketones (substituents = propionic acid and ethyl) yields four pyrroles, which upon subsequent combinatorial reaction afford a distribution of porphyrinogens. A software program for virtual library generation predicts 538 porphyrinogens from this [2 Â 2] reaction (owing to combinations and permutations) of which there are 25 sets of isomers based on condensed formulas of substituents. The collection spans the entire range of polarity enabled by the biosynthesis including uro-(number of carboxylic acids = 8), copro-(4), meso-( 2), and etio-porphyrinogen (0). The first two are successive intermediates in the extant biosynthesis, the latter two resemble in polarity the advanced biosynthetic products protoporphyrin and chlorophyll. Upon consideration of substituent patterns, the porphyrins (obtained by oxidation of the porphyrinogens) can be grouped into one of four polarity categories (predicted percentage): hydrophilic (0.4%), uncertain (83.6%), amphiphilic (15.6%), and hydrophobic (0.4%). HPLC and mass spectrometry data are consistent with expectations to the limit of analytical capabilities. Thus, in terms of the polarity of the tetrapyrrole macrocycles formed, an all-at-once non-enzymic combinatorial process recapitulates features of the stepwise biosynthetic pathway.

Interleukin-4 boosts the capacity of dendritic cells to present endogenous antigens on MHC II and to resist bacterial infection through a mechanism shown to be partially dependent on RUFY4 expression.

Background: MicroRNAs (miRNAs) are a new class of small RNAs of approximately 22 nucleotides in length that control eukaryotic gene expression by fine tuning mRNA translation. They regulate a wide variety of biological processes, namely developmental timing, cell differentiation, cell proliferation, immune response and infection. For this reason, their identification is essential to understand eukaryotic biology. Their small size, low abundance and high instability complicated early identification, however cloning/Sanger sequencing and new generation genome sequencing approaches overcame most technical hurdles and are being used for rapid miRNA identification in many eukaryotes.

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