DOI: 10.1073/pnas.051623398. Internal initiation of translation of five dendritically localized neuronal mRNAs

Internal initiation of translation of five dendritically localized neuronal mRNAs

10.1073/pnas.051623398

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

In neurons, translation of dendritically localized mRNAs is thought to play a role in affecting synaptic efficacy. Inasmuch as components of the translation machinery may be limiting in dendrites, we investigated the mechanisms by which translation of five dendritically localized mRNAs is initiated. The 5′ leader sequences of mRNAs encoding the activity-regulated cytoskeletal protein, the α subunit of calcium–calmodulin-dependent kinase II, dendrin, the microtubule-associated protein 2, and neurogranin (RC3) were evaluated for their ability to affect translation in the 5′ untranslated region of a monocistronic reporter mRNA. In both neural and nonneural cell lines, the activity-regulated cytoskeletal protein, microtubule-associated protein 2, and α-CaM Kinase II leader sequences enhanced translation, whereas the dendrin and RC3 5′ untranslated regions slightly inhibited translation as compared with controls. When cap-dependent translation of these constructs was suppressed by overexpression of a protein that binds the cap-binding protein eIF4E, it was revealed that translation of these mRNAs had both cap-dependent and cap-independent components. The cap-independent component was further analyzed by inserting the 5′ leader sequences into the intercistronic region of dicistronic mRNAs. All five leader sequences mediated internal initiation via internal ribosome entry sites (IRESes). The RC3 IRES was most active and was further characterized after transfection in primary neurons. Although translation mediated by this IRES occurred throughout the cell, it was relatively more efficient in dendrites. These data suggest that IRESes may increase translation efficiency at postsynaptic sites after synaptic activation.

Bibliography

Pinkstaff, J. K., Chappell, S. A., Mauro, V. P., Edelman, G. M., & Krushel, L. A. (2001). Internal initiation of translation of five dendritically localized neuronal mRNAs. Proceedings of the National Academy of Sciences, 98(5), 2770â2775.

Authors 5

Jason K. Pinkstaff (first)
Stephen A. Chappell (additional)
Vincent P. Mauro (additional)
Gerald M. Edelman (additional)
Les A. Krushel (additional)

References 34 Referenced 136

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:45 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:59 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:27 a.m.)
Issued	24 years, 6 months ago (Feb. 20, 2001)
Published	24 years, 6 months ago (Feb. 20, 2001)
Published Online	24 years, 6 months ago (Feb. 20, 2001)
Published Print	24 years, 5 months ago (Feb. 27, 2001)

Funders 0

None

BibTeX

@article{Pinkstaff_2001, title={Internal initiation of translation of five dendritically localized neuronal mRNAs}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.051623398}, DOI={10.1073/pnas.051623398}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Pinkstaff, Jason K. and Chappell, Stephen A. and Mauro, Vincent P. and Edelman, Gerald M. and Krushel, Les A.}, year={2001}, month=feb, pages={2770–2775} }

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