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The Taiwan Precision Medicine Initiative (TPMI) has built a cohort of more than half a million individuals with Han Chinese ancestry, providing a rich resource of genetic and medical data for this group.

RNA is central to many cellular functions, but in vivo structures of most RNAs are unknown. Here Kwok et al. present a universally applicable method, DMS/SHAPE-LMPCR, to identify structures of low-abundance transcripts in living cells, which reveals important features that are uniquely present in vivo.

This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

This Protocol Extension (to an existing SELEX Nature Protocol) introduces RNA G-quadruplex (rG4)-SELEX, a method that generates novel l-RNA aptamers to target rG4 structures that can be applied to inhibit G-quadruplex-mediated interactions.

The anti-leprosy drug clofazimine inhibits coronavirus replication in several cell models and shows potent antiviral activity against SARS-CoV-2 infection in a hamster model, particularly when used in combination with remdesivir.

The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.

Although extrapulmonary complications of different organ systems are recognized in patients with severe COVID19 effects are less well studied. Here, Qiao et al. characterize the pathogenesis of SARS-CoV-2 on bone metabolism in Syrian hamster and find that bone loss is associated with virus-mediated cytokine dysregulation.

The S1/S2 junction of the SARS-CoV-2 Spike protein is emerging as a key factor in virulence and pathogenesis. Here, the authors characterise an attenuated strain of SARS-CoV-2 with deletions in the critical S1/S2 junction and observe enhanced replication, generation of potent adaptive immunity but reduced immunopathology in a hamster model of infection.

Bobo Wing-Yee Mok et al. observe that the Alpha (B.1.1.7) variant of SARS-CoV-2 exhibits increased competitive fitness over earlier lineages at lower doses in a hamster model of viral transmission. Their results suggest that the Alpha variant’s ability to initiate effective infection with a low dose may underlie its ability to rapidly transmit throughout a population.

Difficulties in propagating HRV-C have hindered our understanding of this common respiratory pathogen. Here, authors developed an organoid-based system to reproducibly propagate HRV-C and characterized HRV-C infection in physiologically active respiratory organoids.

Here the authors investigated DHX36-induced RNA structurome changes by conducting Structure-seq and uncovered that DHX36 binding-induced 3’UTR structural accessibility enhances m6A dependent YTHDF1 binding to promote target mRNA degradation.

Here, the authors report the generation of a live but defective SARS-CoV-2 virus that is envelope-deficient and expresses human interferon beta. They show that nasal vaccination enhances mucosal and lung T cell response and provides pan-sarbecovirus protection in small animals.

Hong Kong experienced a severe wave of SARS-CoV-2 in early 2022. Here, the authors use genomic and serosurveillance data and show that this wave was dominated by the Omicron BA.2 sublineage, and that low protective immunity, particularly in older age groups, contributed to its severity.

The safety of CRISPR-Cas9 editing is a concern. Here the authors use whole genomic analysis by 10x linked-read sequencing and optical genome mapping to interrogate the genome integrity after editing: they see large structural variants at on-target sites and unexpected large chromosomal deletions.

Chan et al. report that 3′ UTR splicing is widespread and enhanced across different cancer types and is associated with more advanced tumour progression.

Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

Current seasonal flu vaccines hardly protect against emerging H5N1 such as clade 2.3.4.4b circulating in cattle. Here, the authors show that a single intranasal immunization of DelNS1-H5N1 vaccine candidates provides effective protection and sustained immunity against highly pathogenic avian influenza A viruses.

SARS-CoV-2 variants of concern such as the Omicron variant pose a challenge for vaccination and antibody immunotherapy. Here, Zhou et al. isolate a broadly neutralizing antibody (bNAb), named ZCB11, that protects Golden Syrian hamsters against Omicron. Applying CryoEM the authors show that ZCB11 heavy chain predominantly interacts with RBD in up confirmation, which interferes with ACE2 receptor binding.

During evolution, plants have adapted to habitats with distinct temperature ranges. In this study, scientists report that a specific RNA structure motif, RNA G-quadruplex (RG4) is enriched across genomes of plant species growing in colder climates.

INSIHGT is an affordable, non-destructive and accessible 3D spatial biology method that maps diverse biomolecules deep within tissues, such as proteins and RNA, thus advancing the understanding of complex biological systems on a multi-omics level.

TGF-β stimulated tumor-associated neutrophils (TANs) can exert pro-tumoral functions. Here the authors show that Smad3 activation in TANs is associated with an N2-like polarization state and poor outcome in patients with non-small cell lung carcinoma and that Smad3 targeting reprograms TANs to an antitumor state suppressing tumor growth in preclinical lung cancer models.

Here the authors shows that G-quadruplexes, non-canonical DNA/RNA structures, can have a direct impact on alternative splicing and that binding of splicing regulators is affected by their presence.

Bat and human intestinal organoids can support replication of SARS-CoV-2, enabling further characterization of the virus lifecycle and investigation of potential mechanisms of enteric infection in COVID-19.

Skeletal muscle stem cells (or satellite cells, SCs) are normally quiescent but activate and expand in response to injury. Here the authors show that induction of DHX36 helicase during SC activation promotes mRNA translation by binding to 5′UTR mRNA G-quadruplexes (rG4) in targets including Gnai2 and unwinding them.

A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronavirus disease 2019 (COVID-19).

Using a knock-in strategy to ablate a Cdk5-targeted serine phosphorylation site on residue 478 of the TrkB receptor, the authors demonstrate the role of this phosphorylation in activity-dependent functional and structural plasticity, as well as in learning and memory. They further show that TIAM1 and Rac1 act downstream of TrkB S478 phosphorylation during spine remodeling.

RNA adopts vast and complicated secondary structures in the living cell; reported here is a new approach, structure-seq, that characterises RNA structure in vivo on a genome-wide scale at nucleotide resolution and should be applicable to any organism.

rG4-seq enables the mapping of RNA G-quadruplex structures across entire transcriptomes at nucleotide resolution.

A combination of single-molecule long-read sequencing, single-molecule genome mapping and short-read sequencing provides reference-quality de novo assemblies and also shows improved phasing and variant detection over short-read assemblies when mapping to a reference genome.

Current vaccines are less efficient in preventing infection. Here, the authors show that an intranasal vaccine (DelNS1-RBD) based on a live attenuated influenza virus induces robust levels of neutralizing antibodies and T cells and prevents replication of SARS-CoV-2 Delta and Omicron variants in respiratory tissues.

Structure-seq applies chemically based RNA structure probing on a genome-wide scale, allowing the in vivo structures of thousands of distinct transcripts to be discerned, and the meta-properties of RNA structure–function relationships to be unveiled.

In vivo probing of RNA structures with COMRADES yields insight into RNA folding of the ZIKA virus genome and its interaction with host RNAs.

Prostate-specific antigen is used as a biomarker of prostate cancer, but levels can be affected by other factors not related to cancer. Here, the authors find genes associated with prostate specific antigen levels in healthy men, which could be used to reduce over-diagnosis and over-treatment.