Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle regulation.

MacNicol, Melanie C.; Cragle, Chad E.; MacNicol, Angus M.

doi:10.4161/cc.10.1.14388

Cited by 70 publications

(69 citation statements)

References 36 publications

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“…Although Musashi proteins have been primarily implicated in promoting mammalian stem and progenitor cell self-renewal and proliferation via repression of target mRNAs (e.g. m-Numb and p21) (50 -53), recent findings have emerged demonstrating that Musashi switches from a repressor to an activator of target mRNA translation in response to mammalian neural stem cell differentiation cues (54). A role for Musashi-mediated activation has also been proposed for Robo3/Rig-1 mRNA translation during midline crossing of precerebellar neurons (55) and activation of m-Numb mRNA translation in the gastric mucosa of mice (56), although the underlying mechanisms have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Musashi Protein-directed Translational Activation of Target mRNAs Is Mediated by the Poly(A) Polymerase, Germ Line Development Defective-2

Cragle¹,

MacNicol

2014

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 99%

Musashi Protein-directed Translational Activation of Target mRNAs Is Mediated by the Poly(A) Polymerase, Germ Line Development Defective-2

Cragle¹,

MacNicol

2014

Journal of Biological Chemistry

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“…Moreover, our finding of higher Lgr5 mRNA levels in the distal small intestine of Msi-1-knockout mice again raises the potential for varying roles of Msi-1, dependent on the intestinal region. There are reports that Msi-1 can inhibit or promote translation in a context-dependent manner (MacNicol et al, 2011;Takahashi et al, 2013). One potential mechanism for the differential role of Msi-1 in the two stem cell pools and the different intestinal regions is that features of the stem cell niche or intestinal region dictate whether Msi-1 blocks or promotes translation.…”

Section: Discussionmentioning

confidence: 99%

Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion

Wolfe

Ernlund

McGuinness

et al. 2017

Journal of Cell Science

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Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in a model organism. One such oncogene, Musashi-1 (Msi-1), regulates translation of target mRNAs and is implicated in promoting tumorigenesis in the colon and other tissues. Msi-1 targets include the tumor suppressor adenomatous polyposis coli (Apc), a Wnt pathway antagonist lost in ∼80% of all colorectal cancers. Cell culture experiments have established that Msi-1 is a Wnt target, thus positioning Msi-1 and Apc as mutual antagonists in a mutually repressive feedback loop. Here, we report that intestines from mice lacking Msi-1 display aberrant Apc and Msi-1 mutually repressive feedback, reduced Wnt and Notch signaling, decreased proliferation, and changes in stem cell populations, features predicted to suppress tumorigenesis. Indeed, mice with germline Apc mutations (Apc Min ) or with the Apc 1322T truncation mutation have a dramatic reduction in intestinal polyp number when Msi-1 is deleted. Taken together, these results provide genetic evidence that Msi-1 contributes to intestinal tumorigenesis driven by Apc loss, and validate the pursuit of Msi-1 inhibitors as chemo-prevention agents to reduce tumor burden.

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“…We are not aware of any data demonstrating a specific function for musashi in the notochord in any chordate. However, the ancestral function of these RRM containing proteins may simply be in the switch between undifferentiated/stem cell and differentiated cell types and in the regulation of proliferation (Potten et al, 2003;MacNicol et al, 2011;Hochgreb-Hägele et al, 2014). Supporting this, the anterior endoderm encompassing the zones that will form the mouth and gill slits in amphioxus larvae, which has conspicuous musashi expression, is a zone of extensive proliferation and remodeling (Holland and Holland, 2006).…”

Section: Evolution Of Musashi Related Rrm-containing Proteins and Novmentioning

confidence: 99%

Asymmetric Distribution of pl10 and bruno2, New Members of a Conserved Core of Early Germline Determinants in Cephalochordates

et al. 2016

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Molecular fingerprinting of conserved germline and somatic "stemness" markers in different taxa have been key in defining the mechanism of germline specification ("preformation" or "epigenesis"), as well as expression domains of somatic progenitors. The distribution of molecular markers for primordial germ cells (PGCs), including vasa, nanos, and piwil1, as well as Vasa antibody staining, support a determinative mechanism of germline specification in the cephalochordate Branchiostoma lanceolatum, similarly to other amphioxus species. pl10 and bruno2, but not bruno4/6, are also expressed in a pattern consistent with these other germline genes, adding to our repertoire of PGC markers in lancelets. Expression of nanos, vasa, and the remaining markers (musashi, pufA, pufB, pumilio, and piwil2) may define populations of putative somatic progenitors in the tailbud, the amphioxus posterior growth zone, or zones of proliferative activity. Finally, we also identify a novel expression domain for musashi, a classic neural stem cell marker, during notochord development in amphioxus. These results are discussed in the context of germline determination in other taxa, stem cell regulation, and regenerative capacity in adult amphioxus.

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Context-dependent regulation of Musashi-mediated mRNA translation and cell cycle regulation.

Cited by 70 publications

References 36 publications

Musashi Protein-directed Translational Activation of Target mRNAs Is Mediated by the Poly(A) Polymerase, Germ Line Development Defective-2

Musashi Protein-directed Translational Activation of Target mRNAs Is Mediated by the Poly(A) Polymerase, Germ Line Development Defective-2

Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion

Asymmetric Distribution of pl10 and bruno2, New Members of a Conserved Core of Early Germline Determinants in Cephalochordates

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