The GIGYF proteins associate with 4EHP and RNA-associated proteins to elicit transcript-specific translational repression. However, the mechanism by which the GIGYF1/2-4EHP complex is recruited to its target transcripts remain unclear. Here we report the crystal structures of the GYF domains from GIGYF1 and GIGYF2 in complex with proline-rich sequences from miRISC-binding proteins TNRC6C and TNRC6A, respectively. The TNRC6 proline-rich motifs bind to a conserved array of aromatic residues on the surface of the GIGYF1/2 GYF domain, bridging 4EHP to Argonaute-miRNA mRNA targets. Our structures also reveal a phenylalanine residue conserved from yeast to human GYF domains that contributes to GIGYF2 thermostability. The molecular details we outline here are likely to be conserved between GIGYF1/2 and other RNA-binding proteins to elicit 4EHP-mediated repression in different biological contexts.

The GIGYF proteins interact with 4EHP and RNA-associated proteins to elicit transcript-specific translational repression. However, the mechanism by which the GIGYF1/2–4EHP complex is recruited to its target transcripts remain unclear. Here we report the crystal structures of the GYF domains from GIGYF1 and GIGYF2 in complex with proline-rich sequences from miRISC-binding proteins TNRC6C and TNRC6A, respectively. The TNRC6 proline-rich motifs bind to a conserved array of aromatic residues on the surface of the GIGYF1/2 GYF domain, thereby bridging 4EHP to Argonaute–miRNA complexes. Our structures also reveal a phenylalanine residue conserved from yeast to human GYF domains that contributes to GIGYF2 thermostability. The molecular details we outline here are likely to be conserved between GIGYF1/2 and other RNA-binding proteins to elicit 4EHP-mediated repression in different biological contexts.

COVID-19 transformed the medical school learning environment. How social studying and learning (SSL) may have changed was considered worthy of exploration. This study describes the effect of the learning environment transformation on how SSL is conducted by medical students and the reasoning behind any changes. A post-positivist stance was adopted with a mixed method convergent-parallel approach. An online survey explored the participation rate and nature of SSL and how these related to literature-identified underpinning factors that influence participation in SSL. A follow-up interview explored the survey responses. A total of 87 survey responses were collected. Following exclusion of incomplete responses, 57 responses were analysed, and nine follow-up interviews were conducted. Cross-tabulation and logistic regression were conducted to analyse the quantitative data and thematic analysis was conducted to analyse the qualitative data. No significant difference was observed in SSL participation rate during COVID-19. Students transitioned from in-person to Zoom meetings for sensibility, ease and convenience. Students continued participating in SSL for motivation and began participating for accountability, focus and replacement of lost social interaction. The same content was studied using a wider range of activities. Significant decreases were observed in students’ perception of the effect of a range of factors. The observed changes to SSL during online learning suggest that SSL is integral for many medical students and will be adapted as required. Given that medical school will always involve some periods of online learning, understanding of the nature of and driving factors behind how medical students engage in SSL during online learning may enable medical educators to support all aspects of student learning.