Hfq: the flexible RNA matchmaker

Hfq: the flexible RNA matchmaker

The Matchmaker Exchange API allows searching a patient’s genotypic or phenotypic profiles across clinical sites, for the purposes of cohort discovery and variant-disease causal validation. This API can be used not only to search for matching patients, but also to match against public disease and model organism data. This public disease data enables matching known diseases and variant-phenotype associations using phenotype semantic similarity algorithms developed by the Monarch Initiative. The model data can provide additional evidence to aid diagnosis, suggest relevant models for disease mechanism and treatment exploration, and identify collaborators across the translational divide. The Monarch Initiative provides an implementation of this API for searching multiple integrated sources of data that contextualize the knowledge about any given patient or patient family into the greater biomedical knowledge landscape. While this corpus of data can aid diagnosis, it is also the beginning of research to improve understanding of rare human diseases.

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In the past few years, structures and modeling of wild type Hfq and assays of various mutants have documented that the homohexameric Hfq ring can contact RNA at four sites proximal face, distal face, rim and C-terminal tail and that different RNAs bind to these sites in various configurations. These studies together with novel in vitro and in vivo experimental approaches are beginning to give mechanistic insights into how Hfq acts to promote small RNA-mRNA pairing and indicate that flexibility is integral to the Hfq role in RNA matchmaking.

This broad Hfq role in facilitating base pairing sRNA function is reflected in the pleiotropic phenotypes of hfq deletion strains observed for a variety of bacteria, including stress sensitivity and reduced virulence reviewed in [ 3 ]. Given the central role played by Hfq in sRNA-mediated gene regulation in many bacteria, the protein has been the focus of extensive study. The sequences and structures of Hfq unambiguously show that the protein is a member of the Sm and Sm-like Lsm family of proteins that are involved in various aspects of RNA metabolism in virtually all eukaryotes and archaea reviewed in [ 7 , 8 ].

Two comprehensive reviews about Hfq were published in and [ 2 , 3 ]. However, given the interest in the chaperone, much has been learned about the protein and its mechanisms of promoting RNA base pairing in the past three years.

Use of Model Organism and Disease Databases to Support Matchmaking for Human Disease Gene Discovery

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Destiny: Bungie is discussing matchmaking for Raids

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