Focus |

Focus on regulatory RNAs

RNA molecules have many additional functions beyond their classical role as messengers between DNA and protein. Various RNA types and purposes are implicated in the development, physiology and disease of organisms. Nature Cell Biology presents a Focus of specially commissioned Review articles that discuss the cellular functions of long noncoding RNAs, RNA modifications and their relevance in cancer. An accompanying online library contains research articles and commentaries on this topic published by Nature Cell Biology in the past two years.

Nature Cell Biology Reviews

Yao et al. review functions of lncRNAs in controlling chromatin architecture, transcription and nuclear bodies in the nucleus and in modulating mRNA stability, translation and protein modifications in the cytoplasm.

Review Article | | Nature Cell Biology

Editorial and Comment

RNA molecules are more than messengers between DNA and protein and exhibit rich regulatory functions in development and disease. In this issue, we present a Focus on regulatory RNAs with specially commissioned Review articles that discuss recent advances in this fast-growing area.

Editorial | | Nature Cell Biology

MicroRNAs (miRNAs) repress target mRNAs, often with exquisite tissue specificity. Wang et al. exploit the specific expression of miRNAs to regulate guide production for Cas9. Their method enables novel strategies to simultaneously measure the activity of multiple miRNAs and restrict Cas9 binding or genome editing to precisely defined cell types.

News & Views | | Nature Cell Biology

Stressed eukaryotic cells store mRNAs in protein-rich condensates called stress granules. Using single-molecule tracking techniques to examine how mRNAs enter stress granules, a new study shows that mRNAs make transient contacts with the granule surface before stable association, and become largely immobile after entry.

News & Views | | Nature Cell Biology

The intestinal crypt has become the prototype compartment to investigate adult stem cell biology, and the list of identified intestinal stem cell (ISC) markers is already extensive. A comprehensive study now uncovers an additional layer in ISC regulation by introducing long noncoding RNA lncGata6 to the stem cell repertoire.

News & Views | | Nature Cell Biology

Paraspeckles are nuclear bodies built on the long noncoding RNA, NEAT1, that regulate cellular homeostasis, but how they sense and help under stress is unclear. A study now shows mitochondrial stress modulates paraspeckles by altering NEAT1 expression with a feedback loop that influences mitochondrial homeostasis.

News & Views | | Nature Cell Biology

How the metabolic crosstalk between cancer and stromal cells affects tumour growth is incompletely defined. MYC-activated cancer cells are now shown to secrete exosomal miR-105, which fuels tumour growth by inducing a MYC-dependent metabolic programme in cancer-associated fibroblasts.

News & Views | | Nature Cell Biology

A coordinated DNA damage response mediated by p53 to repair DNA lesions or to promote apoptosis is essential for maintenance of genome stability. A study now unveils the long non-coding RNA GUARDIN as a component of this pathway, which protects genome integrity in a pleiotropic fashion.

News & Views | | Nature Cell Biology

N6-methyladenosine (m6A) mRNA modification influences mRNA fate by stimulating recruitment of m6A reader proteins. A previously unappreciated class of m6A reader proteins is now shown to use a common RNA-binding domain and flanking regions to selectively bind m6A-containing mRNAs, increasing their translation and stability.

News & Views | | Nature Cell Biology

The unfolded protein response (UPR) regulates cell metabolism and survival in response to stress, yet how the UPR is connected to other signalling pathways is poorly understood. PERK is now shown to regulate Bmal1 and Clock proteins to promote cancer cell survival, revealing a link between growth regulation and circadian rhythms.

News & Views | | Nature Cell Biology

Small RNAs generated at DNA break sites are implicated in mammalian DNA repair. Now, a study shows that following the formation of DNA double-strand breaks, bidirectional transcription events adjacent to the break generate small RNAs that trigger the DNA damage response by local RNA:RNA interactions.

News & Views | | Nature Cell Biology

A variety of non-coding RNAs have been reported as endogenous sponges for cancer-modulating miRNAs. However, miRNA trapping by transcripts with protein-coding functions is less understood. The mRNA of TYRP1 is now found to sequester the tumour suppressor miR-16 on non-canonical miRNA response elements in melanoma, thereby promoting malignant growth.

News & Views | | Nature Cell Biology

The mechanism of action of oncogenes in acute myeloid leukaemia is poorly understood. A study now shows that the fusion oncoprotein AML1-ETO regulates leukaemogenesis by increasing the expression of small nucleolar RNAs through post-transcriptional mechanisms, resulting in increased ribosomal RNA methylation, protein translation, and promotion of leukaemic-cell self-renewal and growth.

News & Views | | Nature Cell Biology

Little is known regarding how the interactions of stem cells with the immune system regulate their plasticity. A study now describes a mechanism by which normal breast and cancer stem cells utilize miR-199a to downregulate the corepressor LCOR and minimize responses to type I interferon.

News & Views | | Nature Cell Biology

Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1–HER3 and Hippo–YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.

News & Views | | Nature Cell Biology

Related Nature Cell Biology Research

Consistent crosstalk between cancer cells and stromal cells exists in the tumour microenvironment. Yan et al. show that exosomal miR-105 derived from cancer cells confers metabolic plasticity in recipient cancer-associated fibroblasts to adapt to nutrient-replete and -deplete conditions, thereby sustaining tumour growth.

Article | | Nature Cell Biology

Gilot et al. have found that TYRP1 mRNA, in addition to coding for TYRP1 protein, can promote melanoma by sequestering the tumour suppressor miR-16, thus de-repressing the mRNA transcription of miR-16 target RAB17, which is involved in melanoma cell proliferation.

Article | | Nature Cell Biology