2021-BBSRC/NSF-BIO An autonomous registry system for plant microRNAs

MicroRNAs tiny RNAs that function to regulate other genes in animals and plants. In plants, microRNAs are involved in many biological processes, including development of different plant tissues, and the mechanisms by which plants adapt and respond to stress. In crops, microRNAs have been found to be involved in fertility and yield, and are therefore important molecules to understand for food and agriculture.

The past two decades have seen the discovery of thousands of different microRNA genes. When a new microRNA is discovered, it is vital that it is catalogued, named, and information about it made available to the scientific community. A single central registry and database has existed since 2004 to name and catalogue microRNAs: miRBase (https://www.mirbase.org/). However, the processes by which microRNAs have been named and catalogued have been, until now, time-consuming and labour-intensive. Recently, the pace at which microRNAs have been discovered has overwhelmed the capacity of miRBase to deal with them. Yet the need for a single trusted resource is more acute than ever.

This proposal aims to design and implement a system by which new microRNAs are automatically assessed for the quality of their annotation, named, and deposited in the public miRBase database, focussing first on plant microRNAs. The tools that we produce to annotate new microRNAs will be made freely and publicly available, such that all microRNA biologists can use the same standards for microRNA discovery. This work will therefore enable the continued expansion of the microRNA field.

MicroRNAs (miRNAs) are ~20 to 24 nucleotide RNAs that function to regulate levels of mRNA targets in animals and plants. miRNAs guide RNA-induced silencing complexes (RISCs) to target longer RNAs. The genic targets of miRNAs function in many key cellular processes, including development, biotic and abiotic stress responses. In crop plants, miRNAs have demonstrated roles supporting phenotypes important for fertility and yield, and thus contribute to food security and the agricultural economy.

As with all features of genomes, cataloging and tracking miRNA genes consistently and across genomes using appropriate gene names is crucial. This requires uniform and rigorous assignment of identifiers, periodic reassessment and screening using the latest criteria, and community input. It is crucial that different publications and databases use the same name for a particular miRNA, and homologs in different species should ideally receive consistent names. A single, central registry for miRNA nomenclature and quality control has existed since 2004 to name and catalogue miRNAs: miRBase (http://www.mirbase.org/). The primary curator of miRBase has been co-PI Griffiths-Jones.

miRBase faces challenges in the current era of 'big data'. In particular, registration of new miRNAs currently relies on time-consuming, manual curation. Inexpensive sequencing of genomes and small RNAs has massively increased the discovery rate of miRNAs, exceeding the capacity of miRBase for manual curation of new entries. Yet the need for a single trusted resource is more acute than ever, for rapid registration of new miRNAs, and to assess both existing annotations and new. Plants have multiple small RNA biogenesis pathways that yield similarly-sized sequences, often confounding miRNA identification processes, and resulting in some poor miRNA annotations.