mRNA localization is linked to translation regulation in theCaenorhabditis elegansgerm lineage

Abstract

Caenorhabditis elegans early embryos generate cell-specific transcriptomes despite lacking active transcription, thereby presenting an opportunity to study mechanisms of post-transcriptional regulatory control. We observed that some cell-specific mRNAs accumulate nonhomogenously within cells, localizing to membranes, P granules (associated with progenitor germ cells in the P lineage) and P-bodies (associated with RNA processing). The subcellular distribution of transcripts differed in their dependence on 3′UTRs and RNA binding proteins, suggesting diverse regulatory mechanisms. Notably, we found strong but imperfect correlations between low translational status and P granule localization within the progenitor germ lineage. By uncoupling translation from mRNA localization, we untangled a long-standing question: Are mRNAs directed to P granules to be translationally repressed, or do they accumulate there as a consequence of this repression? We found that translational repression preceded P granule localization and could occur independently of it. Further, disruption of translation was sufficient to send homogenously distributed mRNAs to P granules. These results implicate transcriptional repression as a means to deliver essential maternal transcripts to the progenitor germ lineage for later translation.

C. elegans germ granules require both assembly and localized regulators for mRNA repression

“…They are crucial for fertility and totipotency 8 , and some of their components can display liquid droplet behavior 9 ,– 12 . In the primordial germ cells of the embryo, P granules are proposed to protect mRNAs from small RNA-based regulatory pathways 13 , 14 , and to localize and concentrate mRNAs for robust germline development independent of translational repression 15 , 16 . In adult germ cells, P granules are essential for proper germ cell development 17 , 18 .…”

Protein-based condensation mechanisms drive the assembly of RNA-rich P granules

“…This relocalization correlates with preferential growth of MEG-coated PGL droplets in the posterior and dissolution of ‘naked’ PGL droplets in the anterior side ( Brangwynne et al, 2009 ; Smith et al, 2016 ). In addition to PGL and MEG co-assemblies, P granules also concentrate specific maternal transcripts ( Parker et al, 2020 ; Seydoux and Fire, 1994 ). A survey of mRNAs that immunoprecipitate with PGL-1 and MEG-3 suggests that MEG-3 is most directly responsible for recruiting mRNAs to P granules ( Lee et al, 2020 ).…”

Translation-dependent mRNA localization toCaenorhabditiselegans adherens junctions

“…We conducted an smFISH-based survey, which identified endogenous mRNAs that are localized at or near the cell membrane (five out of twenty-five tested mRNAs). mRNA localization in C. elegans has only been addressed in the early embryo for maternally provided mRNAs (Parker et al, 2020) and synapses in adult neurons (Yan et al, 2009). Previous studies of Drosophila embryogenesis have shown that many mRNAs are localized subcellularly, including mRNAs coding for cytoskeletal and junctional components (Jambor et al, 2015;Lecuyer et al, 2007;Ryder & Lerit, 2018).…”