Inter-dependent Centrosomal Co-localization of the cen and ik2 cis-Natural Antisense mRNAs in Drosophila

Abstract

Highlights d The cen and ik2 cis-NAT mRNAs co-localize to centrosomes in Drosophila embryos d Loss of cen disrupts ik2 centrosomal localization, revealing a targeting co-dependency d Centrosomal co-localization requires interactions between the 3 0 UTRs of cen and ik2 d Subcellular fractionation data reveal that cis-NATs often localize to similar sites

Think globally, act locally: Centrosome-localized mRNAs ensure mitotic fidelity

“…They generated chimeric c9UTR transgenes that target cen mRNA to the anterior pole while depleting it from the middle of the embryo. These experiments showed that the cen coding sequence was sufficient to target cen mRNA to centrosomes, consistent with previous studies (9), where they accumulated at the anterior pole and sequestered FMRP. Consequently, the loss of cen mRNA and Cen protein in the middle of the embryo caused by mistargeting to the anterior pole led to abnormal spindles in nearly half the embryos examined.…”

“…Interestingly, some centrosome-associated mRNAs were found as single molecules, while others were organized in granules. Consistent with a recent study (9), cen mRNA formed micron-scale granules that were enriched with centrosomes during interphase compared with metaphase (60% versus 25%) and exhibited a bias toward the mother centrosome. The latter could be explained by the mother centrosome having a larger PCM with a higher content of Cnn scaffolding protein.…”

Quantitative analysis of subcellular distributions with an open-source, object-based tool

“…Work from our lab and others recently showed that centrocortin ( cen ) mRNA forms local enrichments near centrosomes, unlike the metabolic enzyme gapdh ( Fig. 2 A,B) ( Bergalet et al, 2020 ; Lécuyer et al, 2007 ; Ryder et al, 2020 preprint).

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A choreography of centrosomal mRNAs reveals a conserved localization mechanism involving active polysome transport

“…In the following study, 13 mRNAs were annotated as enriched on Drosophila centrosomes in at least one stage or tissue over the full course of embryogenesis 32 . Finally, two natural antisense mRNAs (cen and ik2) were recently shown to co-localize to centrosomes in a co-dependent manner via 3′ UTR interactions in Drosophila embryos 33 . In humans, four mRNAs (PCNT, HMMR, ASPM, and NUMA1), and two translation factors (eIF4E and the phosphorylated ribosomal protein p-RPS6) were recently found to localize at centrosomes 8,24 .…”