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Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

ABSTRACT: Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

PROVIDER: PRJNA507419 | ENA |

REPOSITORIES: ENA

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Makorin 1 controls embryonic patterning by alleviating Bruno-mediated repression of oskar translation

Project description:Makorins are an evolutionary conserved family of proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. Previous analysis indicated a maternal role for Makorin 1 (Mkrn1) in Drosophila embryonic patterning and germ cell specification, but the underlying mechanism has remained elusive. Here, we show that Mkrn1 is specifically required for translational activation of oskar, which encodes a critical regulator of axis specification and germ plasm assembly. We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and specifically binds osk 3’ UTR adjacent to A-rich sequences. The binding of Mkrn1 to osk 3’UTR occurs in a region that overlaps with Bruno responsive elements (BRE), previously shown to have a dual role in regulating osk translation. We observe an increased association of the translational repressor Bruno (Bru) with osk mRNA upon depletion of Mkrn1, implying that both proteins compete with each other for osk binding. Consistently, reducing Bru dosage is sufficient to partially rescue osk translation and the embryonic lethality associated with Mkrn1 alteration. Thus, we conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation via displacing Bru from its 3’ UTR

2020-01-29 | PXD011802 | Pride

Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

Project description:Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar (osk). We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in regions overlapping with Bruno1 (Bru1) responsive elements (BREs) that regulate osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR.

2020-01-06 | GSE123052 | GEO

Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation

Project description:Makorins are evolutionary conserved proteins that contain C3H-type zinc finger modules and a RING E3 ubiquitin ligase domain. In Drosophila maternal Makorin 1 (Mkrn1) has been linked to embryonic patterning but the mechanism remained unsolved. Here, we show that Mkrn1 is essential for axis specification and pole plasm assembly by translational activation of oskar. We demonstrate that Mkrn1 interacts with poly(A) binding protein (pAbp) and binds specifically to osk 3’ UTR in regions overlapping Bruno1 (Bru1) responsive elements (BREs), which regulate osk translation. We observe increased association of the translational repressor Bru1 with osk mRNA upon depletion of Mkrn1, indicating that both proteins compete for osk binding. Consistently, reducing Bru1 dosage partially rescues viability and Osk protein level in ovaries from Mkrn1 females. We conclude that Mkrn1 controls embryonic patterning and germ cell formation by specifically activating osk translation, most likely by competing with Bru1 to bind to osk 3’ UTR.

2022-10-17 | GSE139030 | GEO

Makorin 1 controls embryonic patterning by alleviating Bruno1-mediated repression of oskar translation.

Project description: Not available

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Patterning the embryonic pulmonary mesenchyme

Project description:Patterning the embryonic pulmonary mesenchyme

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Controlling tissue patterning by translational regulation of signaling transcripts through the core translation factor eIF3c [II]

Project description:Although gene expression is tightly regulated during embryonic development, the impact of translational control has received less experimental attention. Here, we find that eukaryotic translation initiation factor-3 (eIF3) is required for Shh-mediated tissue patterning. Analysis of loss-of-function eIF3 subunit c (Eif3c) mice reveal a unique sensitivity to the Shh receptor Patched 1 (Ptch1) dosage. Genome-wide in vivo enhanced cross-linking immunoprecipitation sequence (eCLIP-seq) shows unexpected specificity for eIF3 binding to a pyrimidine rich motif present in subsets of 5’-UTRs and a corresponding change in the translation of these transcripts by ribosome profiling in Eif3c loss-of-function embryos. We further find that while Eif3c loss-of-function embryos do not show a global decrease in protein synthesis, translation of Ptch1 through this pyrimidine rich motif is specifically sensitive to eIF3 amount. Altogether, this work uncovers hidden specificity of housekeeping translation initiation machinery for the translation of key developmental signaling transcripts.

2021-09-30 | GSE183471 | GEO

Controlling tissue patterning by translational regulation of signaling transcripts through the core translation factor eIF3c [I]

2021-09-30 | GSE183470 | GEO

PQN-59 antagonizes microRNA-mediated repression during post-embryonic temporal patterning and modulates translation and stress granule formation in C. elegans.

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Gibbin (AHDC1) mesodermal regulation controls epithelial patterning

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Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis.

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