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MicroRNA maturation is initiated by the Microprocessor that cleaves primary microRNA hairpins. Here, the authors uncover distinct roles of two auxiliary factors of the Microprocessor, ERH and SAFB2, in the processing of suboptimal clustered microRNA hairpins.

The authors identify a human cytomegalovirus long non-coding RNA, RNA4.9, that interacts with cGAS and prevents its activation in the nucleus, thereby suppressing virus-induced IFN expression and antiviral activity.

A systematic screen identifies RNA elements that enhance the stability and translation of base-modified mRNA.

The initial immune response following mRNA vaccine injection is not entirely clear. Here, the authors comprehensively profile injection site responses using single-cell transcriptomics in a mouse model showing activation of major axes of innate immune responses upon and the role of IFN-β to promote cellular immunity.

miRNAs are loaded into Argonaute protein and repress complementary mRNA targets. Here the authors show the unappreciated role of RNA binding proteins for efficient miRNA targeting and expand the current understanding of miRNA targeting.

Mixed tailing of hepatitis B virus and human cytomegalovirus transcripts via recruitment of the TENT4–ZCCHC14 complex by a common RNA element protects viral RNAs from degradation.

RNA-protein interactions play critical roles in post-transcriptional gene regulation. Here the authors demonstrate pRBS-ID, an updated MS/MS-based method that combines the benefits of photoactivatable ribonucleosides and the chemical cleavage of RNA.

The active-state structure of human DICER bound to pre-miRNA reveals the structural basis for the specificity of DICER in how it selects substrates in a sequence dependent manner, and sheds light on DICER-related diseases.

Telomeres can be maintained by a telomerase-independent mechanism called an alternative lengthening of telomeres (ALT). Here the authors use mouse Terc (telomerase RNA) knockout embryonic cells and provide longitudinal analysis of ALT telomeres maintained with non-telomeric sequences.

Massively parallel assays reveal a highly conserved sequence motif termed the GYM motif, which potentiates RNA interference by directing Dicer-mediated small RNA processing.

Viral microRNAs can modulate a variety of host genes. Ahn and colleagues identify a human cytomegalovirus microRNA that downregulates the peptide-processing enzyme ERAP1 and prevents presentation of antigenic viral peptides.

Park and colleagues found that LARP1 protects mRNA by forming a complex with PABP on short poly(A) tails of ~30–60 nt and thereby serving as a barricade against deadenylases.

L1 is a group of active retrotransposons in humans. Here the authors show that m⁶A modifications on L1 RNA increase translation efficiency and retrotransposition in human cells. M⁶A motifs are more enriched in evolutionary young L1s.

Here, using mathematical modeling and an in vitro deadenylation system, the authors quantitatively demonstrate the effect of non-adenosines in the poly(A) tail and exemplify how tail sequence regulates mRNA stability.

Cas13 can be harnessed for RNA knockdown and editing in mammalian cells, opening up a range of applications in RNA biology.

Long non-coding RNAs or lincRNAs identified in embryonic stem (ES) cells have been shown to regulate ES cell states; however, how these lincRNAs are regulated remains unclear. Here the authors show that the transcriptional coactivator Pontin regulates the expression of lincRNAs involved in ES cell maintenance in an Oct4-dependent manner.

The transcription factor and tumor suppressor p53 is central to many stress responses and is the target of multiple regulators. The regulatory subunit of PI3 kinase, p85α and CDC42 are now both found to be targets of the miR-29 microRNAs. As p85α and CDC42 are repressors of p53, these miRNAs indirectly activate p53 and thus apoptosis.

Embryonic stem (ES) cells undergo rapid cell division without compromising their ability to differentiate into virtually all cell types. Using ES cells deficient for a microRNA biogenesis factor, Dgcr8, a new report uncovers the importance of specific microRNAs in the ES cell cycle transition from G1 to S phase.

Recent progress in high-throughput sequencing has uncovered an astounding landscape of small RNAs in eukaryotic cells. Various small RNAs can be classified into three classes based on their biogenesis mechanism and the type of Argonaute protein that they are associated with.

In animals, microRNAs (miRNAs) are ∼22 nucleotides in length and are produced by two RNase III proteins — Drosha and Dicer. Their biogenesis is regulated at multiple levels, including at the level of miRNA transcription; by Drosha and Dicer processing; by their modification through RNA editing, RNA methylation, uridylation and adenylation; Argonaute loading; and by RNA decay.

MicroRNAs are potentially powerful biomarkers, though clinical use requires rapid and reliable profiling. Here the authors report amplification-free multicolour single-molecule imaging with single base mismatch sensitivity.

RBS-ID, a method to identify RNA–protein interactions by crosslinking, uses hydrofluoride to cleave RNA to simple mono-nucleoside adducts, which improves coverage and resolution of RNA binding site identification.

A transcription activator–like effector nuclease (TALEN)-mediated knockout approach to delete human microRNA (miRNA) genes was used to generate a library of 540 TALEN pairs for 274 miRNA loci. As a case study, single and double knockouts for two related miRNAs, miR-141 and miR-200c, revealed intriguing functional differences.

RNA uridylation offers a basis for diverse post-transcriptional regulation. Two recent studies reveal new roles of uridylation in immune defense against viruses and retrotransposons.

MicroRNAs (miRNAs) are small non-coding RNAs that induce RNA silencing. Advances in high-throughput and structural studies have provided new insights into animal miRNA biogenesis mediated by RNA–protein interactions, miRNA tailing (uridylation or adenylation) and RNA modifications, and have increased our understanding of miRNA target recognition and target-directed miRNA decay.

A mRNA-interactome capture approach in embryonic stem cells (ESCs) has led to the identification of 283 novel RNA-binding protein (RBP) candidates, of which 68 are preferentially expressed in ESCs. Validation of two known E3 ubiquitin ligases as RBPs reveals an intriguing potential link between RNA biology and protein-modification pathways.

The non-canonical addition of non-templated nucleotides to RNA 3′ ends (tailing) by terminal nucleotidyltransferases includes uridylation, mixed-nucleotide tailing and post-transcriptional polyadenylation. Recent studies of human terminal nucleotidyltransferases have revealed their distinct specificities for substrates, including mRNAs, microRNAs and other non-coding RNAs, and how they control RNA stability and activity.