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Development July 1, 2011; 138 (14): 3079-90.

hnRNP K post-transcriptionally co-regulates multiple cytoskeletal genes needed for axonogenesis.

The RNA-binding protein, hnRNP K, is essential for axonogenesis. Suppressing its expression in Xenopus embryos yields terminally specified neurons with severely disorganized microtubules, microfilaments and neurofilaments, raising the hypothesis that hnRNP K post-transcriptionally regulates multiple transcripts of proteins that organize the axonal cytoskeleton. To identify downstream candidates for this regulation, RNAs that co-immunoprecipitated from juvenile brain with hnRNP K were identified on microarrays. A substantial number of these transcripts were linked to the cytoskeleton and to intracellular localization, trafficking and transport. Injection into embryos of a non-coding RNA bearing multiple copies of an hnRNP K RNA-binding consensus sequence found within these transcripts largely phenocopied hnRNP K knockdown, further supporting the idea that it regulates axonogenesis through its binding to downstream target RNAs. For further study of regulation by hnRNP K of the cytoskeleton during axon outgrowth, we focused on three validated RNAs representing elements associated with all three polymers - Arp2, tau and an α-internexin-like neurofilament. All three were co-regulated post-transcriptionally by hnRNP K, as hnRNP K knockdown yielded comparable defects in their nuclear export and translation but not transcription. Directly knocking down expression of all three together, but not each one individually, substantially reproduced the axonless phenotype, providing further evidence that regulation of axonogenesis by hnRNP K occurs largely through pleiotropic effects on cytoskeletal-associated targets. These experiments provide evidence that hnRNP K is the nexus of a novel post-transcriptional regulatory module controlling the synthesis of proteins that integrate all three cytoskeletal polymers to form the axon.

PubMed ID: 21693523
Article link: Development

Species referenced: Xenopus
Genes referenced: actl6a actr2 aicda hnrnpc hnrnpk mapt mark3 nefm neurog1 neurog2 neurog3 nif pard3 pard6b pkm prph tubb2b
Antibodies: Hnrnpk Ab1 Mapt Ab1 Mark3 Ab1 Nefm Ab1 Nif Ab1 Pard3 Ab1 Tubb2b Ab3
Morpholinos: hnrnpk MO3 mapt MO1 nif MO1

GEO Series: GSE25207: NCBI

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