Biology subjects

Garret, C.

Publications and source records attributed to Garret, C..

3 recordsLinked to original sources

bioRxiv2023

Germ granule higher-order organization coordinates their different functions

Most RNP condensates are composed of heterogeneous immiscible phases. However, how this multiphase organization contributes to their biological functions remains largely unexplored. Drosophila germ granules, a class of RNP condensates, are the site of mRNA storage and translational activation. Here, using super-resolution microscopy and single-molecule imaging approaches, we show that germ granules have a biphasic organization and that translation occurs in the outer phase and at the surface of the granules. The localization, directionality and compaction of mRNAs within the granule depend on their translation status, translated mRNAs being enriched in the outer phase with their 5end oriented towards the surface. Altering germ granule biphasic organization represses translation. These findings demonstrate the importance of RNA granule architecture in organizing different functions, highlighting the functional compartmentalization of RNA granules and the key role of higher-order organization.

cell biology↗

bioRxiv2023

piRNAs are regulators of metabolic reprogramming in stem cells

Stem cells preferentially use glycolysis instead of oxidative phosphorylation and this metabolic rewiring plays an instructive role in their fate; however, the underlying molecular mechanisms remain largely unexplored. PIWI-interacting RNAs (piRNAs) and PIWI proteins have essential functions in a range of adult stem cells across species. Here, we show that piRNAs and the PIWI protein Aubergine (Aub) are instrumental in activating glycolysis in Drosophila germline stem cells (GSCs). High glycolysis is required for GSC self-renewal and aub loss-of-function induces a metabolic switch in GSCs leading to their differentiation. Aub directly binds glycolytic mRNAs and Enolase mRNA regulation by Aub depends on its 5UTR. Furthermore, deletion of a piRNA target site in Enolase 5UTR leads to GSC loss. These data reveal an Aub/piRNA function in translational activation of glycolytic mRNAs in GSCs, and pinpoint a new mode of regulation of metabolic reprogramming in stem cells based on small RNAs.

developmental biology↗

bioRxiv2019

The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm

Piwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. In Drosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base-pairing, leading to both their destabilization in the soma, and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation of nanos mRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A) binding protein PABP and the translation initiation factor eIF3. Polysome gradient profiling identifies Aub role at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promote nanos translation. These results reveal a new mode of mRNA regulation by Aub, highlighting PIWI protein versatility in mRNA regulation.

developmental biology↗