Regulation of axonal trafficking of cytochrome c oxidase IV mRNA

Aschrafi, Armaz; Natera-Naranjo, Orlangie; Gioio, Anthony E.; Kaplan, Barry B.

doi:10.1016/j.mcn.2010.01.009

Cited by 61 publications

(74 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with a critical role played by hairpin stem-loop secondary structures in mediating RNA trafficking (Chartrand et al 1999;Jambhekar and DeRisi 2007;Aschrafi et al 2010;Meer et al 2012).…”

Section: Discussionsupporting

confidence: 85%

“…The 3 ′ UTR of TH mRNA mediates reporter mRNA trafficking to axons mRNA trafficking and localization have been shown to be directed by cis-acting elements often found in the 3 ′ UTR of the mRNA (Martin and Zukin 2006;Jambhekar and DeRisi 2007;Aschrafi et al 2010). Comparative sequence analysis of the 3 ′ UTR of TH revealed that there are several evolutionary conserved regions that may contain regulatory elements (Fig.…”

Section: Local Synthesis Of Th Facilitates Axonal Dopamine Productionmentioning

confidence: 99%

“…These axonal mRNAs code for several functional categories of proteins including cytoskeletal elements, ribosomal proteins, and translation factors, as well as metabolic enzymes and nuclear-encoded mitochondrial mRNAs (for review, see Kaplan et al 2009). The targeting of specific mRNAs to the distal structural/functional domains of the neuron is driven by sequences located in the RNA itself (cis-acting elements), that are often found in the 3 ′ untranslated region (UTR) of the mRNA (Jambhekar and DeRisi 2007;Aschrafi et al 2010;Doyle and Kiebler 2011;Meer et al 2012).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons

Gervasi

Scott

Aschrafi

et al. 2016

RNA

Self Cite

View full text Add to dashboard Cite

Synthesis and regulation of catecholamine neurotransmitters in the central nervous system are implicated in the pathogenesis of a number of neuropsychiatric disorders. To identify factors that regulate the presynaptic synthesis of catecholamines, we tested the hypothesis that the rate-limiting enzyme of the catecholamine biosynthetic pathway, tyrosine hydroxylase (TH), is locally synthesized in axons and presynaptic nerve terminals of noradrenergic neurons. To isolate pure axonal mRNA and protein, rat superior cervical ganglion sympathetic neurons were cultured in compartmentalized Campenot chambers. qRT-PCR and RNA in situ hybridization analyses showed that TH mRNA is present in distal axons. Colocalization experiments with nerve terminal marker proteins suggested that both TH mRNA and protein localize in regions of the axon that resemble nerve terminals (i.e., synaptic boutons). Analysis of polysome-bound RNA showed that TH mRNA is present in polysomes isolated from distal axons. Metabolic labeling of axonally synthesized proteins labeled with the methionine analog, L-azidohomoalanine, showed that TH is locally synthesized in axons. Moreover, the local transfection and translation of exogenous TH mRNA into distal axons facilitated axonal dopamine synthesis. Finally, using chimeric td-Tomato-tagged constructs, we identified a sequence element within the TH 3 ′ UTR that is required for the axonal localization of the reporter mRNA. Taken together, our results provide the first direct evidence that TH mRNA is trafficked to the axon and that the mRNA is locally translated. These findings raise the interesting possibility that the biosynthesis of the catecholamine neurotransmitters is locally regulated in the axon and/or presynaptic nerve terminal.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Local Synthesis Of Th Facilitates Axonal Dopamine Productionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons

Gervasi

Scott

Aschrafi

et al. 2016

RNA

Self Cite

View full text Add to dashboard Cite

show abstract

“…These data show that axons isolated from embryonic and adult rat DRG neurons are enriched in protein synthesis, mitochondrial, and neurite growth-related mRNAs that appear to be common critical elements found in other types of axons (Chun et al 1995(Chun et al , 1997Bassell et al 1998;Eng et al 1999;Zheng et al 2001;Gioio et al 2004;Willis et al 2005Willis et al , 2007Wu et al 2005;Leung et al 2006;Aschrafi et al 2008Aschrafi et al , 2010Taylor et al 2009;Andreassi et al 2010). …”

Section: The Repertoire Of Axonal Mrnas Changes Between Embryonic Andmentioning

confidence: 67%

Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization

Gumy¹,

Yeo²,

Tung³

et al. 2010

RNA

334

401

View full text Add to dashboard Cite

mRNAs are transported, localized, and translated in axons of sensory neurons. However, little is known about the full repertoire of transcripts present in embryonic and adult sensory axons and how this pool of mRNAs dynamically changes during development. Here, we used a compartmentalized chamber to isolate mRNA from pure embryonic and adult sensory axons devoid of non-neuronal or cell body contamination. Genome-wide microarray analysis reveals that a previously unappreciated number of transcripts are localized in sensory axons and that this repertoire changes during development toward adulthood. Embryonic axons are enriched in transcripts encoding cytoskeletal-related proteins with a role in axonal outgrowth. Surprisingly, adult axons are enriched in mRNAs encoding immune molecules with a role in nociception. Additionally, we show Tubulin-beta3 (Tubb3) mRNA is present only in embryonic axons, with Tubb3 locally synthesized in axons of embryonic, but not adult neurons where it is transported, thus validating our experimental approach. In summary, we provide the first complete catalog of embryonic and adult sensory axonal mRNAs. In addition we show that this pool of axonal mRNAs dynamically changes during development. These data provide an important resource for studies on the role of local protein synthesis in axon regeneration and nociception during neuronal development.

show abstract

“…Localisation elements mediating the subcellular distribution of mRNAs are commonly found within 3' UTRs (Andreassi et al, 2010;Aschrafi et al, 2010;Brittis et al, 2002;Kislauskis et al, 1994;Mili et al, 2008;Wu et al, 2005). In fact, the 3' UTR of the mouse RAB13 orthologue has been shown to localise transcripts to protrusion of mouse fibroblasts (Mili et al, 2008) using the MS2 system developed by the Singer lab (Bertrand et al, 1998), but the specific "zipcode" sequence responsible is unknown.…”

Section: Identification Of a Rab13 Mrna Zipcode Sequence That Localismentioning

confidence: 99%

mRNA compartmentalisation spatially orients tissue morphogenesis

Costa

Bradbury

Tarannum

et al. 2018

Preprint

View full text Add to dashboard Cite

SUMMARYThe subcellular distribution of mRNAs is a fundamental biological mechanism implicated in the spatial regulation of gene expression in many cellular contexts. However, whether mRNA localisation contributes to complex morphogenetic processes underpinning tissue development remains unknown.We focused on a model transcript, RAB13, and demonstrated how it is preferentially localised to and locally translated at the leading edge of migrating endothelial cells. We generated a novel MS2-GFPnls zebrafish reporter strain and use the 3' UTR of RAB13 to show, for the first time, tissuespecific visualisation of a localised RNA in migratory cell processes in a living vertebrate organism.Moreover, after mutating the endogenous 3' UTR of RAB13 to disrupt transcript localisation in-vivo, we report altered formation of endothelial cell protrusions within sprouting vessels. Hence, we demonstrate the involvement of mRNA localisation in endothelial cell migration during angiogenesis and are the first to reveal that subcellular transcript distribution modulates tissue morphogenesis.

show abstract

Regulation of axonal trafficking of cytochrome c oxidase IV mRNA

Cited by 61 publications

References 36 publications

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons

The local expression and trafficking of tyrosine hydroxylase mRNA in the axons of sympathetic neurons

Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization

mRNA compartmentalisation spatially orients tissue morphogenesis

Contact Info

Product

Resources

About