Repeat-element RNAs integrate a neuronal growth circuit

Eitan Erez Zahavi; Indrek Koppel; Riki Kawaguchi; Juan A. Oses-Prieto; Adam Briner; Aboozar Monavarfeshani; Irene Dalla Costa; Erna van Niekerk; Jinyoung Lee; Samaneh Matoo; Shane Hegarty; Ryan J. Donahue; Pabitra K. Sahoo; Shifra Ben-Dor; Ester Feldmesser; Julia Ryvkin; Dena Leshkowitz; Rotem Ben Tov Perry; Yuyan Cheng; Eli Farber; Ofri Abraham; Nitzan Samra; Nataliya Okladnikov; Stefanie Alber; Christin A. Albus; Ida Rishal; Igor Ulitsky; Mark H. Tuszynski; Jeffery L. Twiss; Zhigang He; Alma L. Burlingame; Mike Fainzilber

doi:10.1016/j.cell.2025.04.030

Repeat-element RNAs integrate a neuronal growth circuit

Eitan Erez Zahavi, Indrek Koppel, Riki Kawaguchi, Juan A. Oses-Prieto, Adam Briner, Aboozar Monavarfeshani, Irene Dalla Costa, Erna van Niekerk, Jinyoung Lee, Samaneh Matoo, Shane Hegarty, Ryan J. Donahue, Pabitra K. Sahoo, Shifra Ben-Dor, Ester Feldmesser, Julia Ryvkin, Dena Leshkowitz, Rotem Ben Tov Perry, Yuyan Cheng, Eli FarberOfri Abraham, Nitzan Samra, Nataliya Okladnikov, Stefanie Alber, Christin A. Albus, Ida Rishal, Igor Ulitsky, Mark H. Tuszynski, Jeffery L. Twiss, Zhigang He, Alma L. Burlingame, Mike Fainzilber

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

Neuronal growth and regeneration are regulated by local translation of mRNAs in axons. We examined RNA polyadenylation changes upon sensory neuron injury and found upregulation of a subset of polyadenylated B2-SINE repeat elements, hereby termed GI-SINEs (growth-inducing B2-SINEs). GI-SINEs are induced from ATF3 and other AP-1 promoter-associated extragenic loci in injured sensory neurons but are not upregulated in lesioned retinal ganglion neurons. Exogenous GI-SINE expression elicited axonal growth in injured sensory, retinal, and corticospinal tract neurons. GI-SINEs interact with ribosomal proteins and nucleolin, an axon-growth-regulating RNA-binding protein, to regulate translation in neuronal cytoplasm. Finally, antisense oligos against GI-SINEs perturb sensory neuron outgrowth and nucleolin-ribosome interactions. Thus, a specific subfamily of transposable elements is integral to a physiological circuit linking AP-1 transcription with localized RNA translation.

Original language	English
Journal	Cell
Early online date	16 May 2025
DOIs	https://doi.org/10.1016/j.cell.2025.04.030
State	Published Online - 16 May 2025

Keywords

RNA localization
Short Interspersed Nuclear Elements
axon growth
axonal transport
local translation
nerve injury
neuronal length sensing
non-coding RNA

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

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10.1016/j.cell.2025.04.030License: CC BY-NC-ND

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Zahavi, E. E., Koppel, I., Kawaguchi, R., Oses-Prieto, J. A., Briner, A., Monavarfeshani, A., Dalla Costa, I., van Niekerk, E., Lee, J., Matoo, S., Hegarty, S., Donahue, R. J., Sahoo, P. K., Ben-Dor, S., Feldmesser, E., Ryvkin, J., Leshkowitz, D., Perry, R. B. T., Cheng, Y., ... Fainzilber, M. (2025). Repeat-element RNAs integrate a neuronal growth circuit. Cell. Advance online publication. https://doi.org/10.1016/j.cell.2025.04.030

@article{ee428d1c08e646d4a348346f85989eb1,

title = "Repeat-element RNAs integrate a neuronal growth circuit",

abstract = "Neuronal growth and regeneration are regulated by local translation of mRNAs in axons. We examined RNA polyadenylation changes upon sensory neuron injury and found upregulation of a subset of polyadenylated B2-SINE repeat elements, hereby termed GI-SINEs (growth-inducing B2-SINEs). GI-SINEs are induced from ATF3 and other AP-1 promoter-associated extragenic loci in injured sensory neurons but are not upregulated in lesioned retinal ganglion neurons. Exogenous GI-SINE expression elicited axonal growth in injured sensory, retinal, and corticospinal tract neurons. GI-SINEs interact with ribosomal proteins and nucleolin, an axon-growth-regulating RNA-binding protein, to regulate translation in neuronal cytoplasm. Finally, antisense oligos against GI-SINEs perturb sensory neuron outgrowth and nucleolin-ribosome interactions. Thus, a specific subfamily of transposable elements is integral to a physiological circuit linking AP-1 transcription with localized RNA translation.",

keywords = "RNA localization, Short Interspersed Nuclear Elements, axon growth, axonal transport, local translation, nerve injury, neuronal length sensing, non-coding RNA",

author = "Zahavi, \{Eitan Erez\} and Indrek Koppel and Riki Kawaguchi and Oses-Prieto, \{Juan A.\} and Adam Briner and Aboozar Monavarfeshani and \{Dalla Costa\}, Irene and \{van Niekerk\}, Erna and Jinyoung Lee and Samaneh Matoo and Shane Hegarty and Donahue, \{Ryan J.\} and Sahoo, \{Pabitra K.\} and Shifra Ben-Dor and Ester Feldmesser and Julia Ryvkin and Dena Leshkowitz and Perry, \{Rotem Ben Tov\} and Yuyan Cheng and Eli Farber and Ofri Abraham and Nitzan Samra and Nataliya Okladnikov and Stefanie Alber and Albus, \{Christin A.\} and Ida Rishal and Igor Ulitsky and Tuszynski, \{Mark H.\} and Twiss, \{Jeffery L.\} and Zhigang He and Burlingame, \{Alma L.\} and Mike Fainzilber",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = may,

day = "16",

doi = "10.1016/j.cell.2025.04.030",

language = "الإنجليزيّة",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

}

Zahavi, EE, Koppel, I, Kawaguchi, R, Oses-Prieto, JA, Briner, A, Monavarfeshani, A, Dalla Costa, I, van Niekerk, E, Lee, J, Matoo, S, Hegarty, S, Donahue, RJ, Sahoo, PK, Ben-Dor, S, Feldmesser, E, Ryvkin, J, Leshkowitz, D, Perry, RBT, Cheng, Y, Farber, E, Abraham, O, Samra, N, Okladnikov, N, Alber, S, Albus, CA, Rishal, I, Ulitsky, I, Tuszynski, MH, Twiss, JL, He, Z, Burlingame, AL & Fainzilber, M 2025, 'Repeat-element RNAs integrate a neuronal growth circuit', Cell. https://doi.org/10.1016/j.cell.2025.04.030

TY - JOUR

T1 - Repeat-element RNAs integrate a neuronal growth circuit

AU - Zahavi, Eitan Erez

AU - Koppel, Indrek

AU - Kawaguchi, Riki

AU - Oses-Prieto, Juan A.

AU - Briner, Adam

AU - Monavarfeshani, Aboozar

AU - Dalla Costa, Irene

AU - van Niekerk, Erna

AU - Lee, Jinyoung

AU - Matoo, Samaneh

AU - Hegarty, Shane

AU - Donahue, Ryan J.

AU - Sahoo, Pabitra K.

AU - Ben-Dor, Shifra

AU - Feldmesser, Ester

AU - Ryvkin, Julia

AU - Leshkowitz, Dena

AU - Perry, Rotem Ben Tov

AU - Cheng, Yuyan

AU - Farber, Eli

AU - Abraham, Ofri

AU - Samra, Nitzan

AU - Okladnikov, Nataliya

AU - Alber, Stefanie

AU - Albus, Christin A.

AU - Rishal, Ida

AU - Ulitsky, Igor

AU - Tuszynski, Mark H.

AU - Twiss, Jeffery L.

AU - He, Zhigang

AU - Burlingame, Alma L.

AU - Fainzilber, Mike

PY - 2025/5/16

Y1 - 2025/5/16

N2 - Neuronal growth and regeneration are regulated by local translation of mRNAs in axons. We examined RNA polyadenylation changes upon sensory neuron injury and found upregulation of a subset of polyadenylated B2-SINE repeat elements, hereby termed GI-SINEs (growth-inducing B2-SINEs). GI-SINEs are induced from ATF3 and other AP-1 promoter-associated extragenic loci in injured sensory neurons but are not upregulated in lesioned retinal ganglion neurons. Exogenous GI-SINE expression elicited axonal growth in injured sensory, retinal, and corticospinal tract neurons. GI-SINEs interact with ribosomal proteins and nucleolin, an axon-growth-regulating RNA-binding protein, to regulate translation in neuronal cytoplasm. Finally, antisense oligos against GI-SINEs perturb sensory neuron outgrowth and nucleolin-ribosome interactions. Thus, a specific subfamily of transposable elements is integral to a physiological circuit linking AP-1 transcription with localized RNA translation.

AB - Neuronal growth and regeneration are regulated by local translation of mRNAs in axons. We examined RNA polyadenylation changes upon sensory neuron injury and found upregulation of a subset of polyadenylated B2-SINE repeat elements, hereby termed GI-SINEs (growth-inducing B2-SINEs). GI-SINEs are induced from ATF3 and other AP-1 promoter-associated extragenic loci in injured sensory neurons but are not upregulated in lesioned retinal ganglion neurons. Exogenous GI-SINE expression elicited axonal growth in injured sensory, retinal, and corticospinal tract neurons. GI-SINEs interact with ribosomal proteins and nucleolin, an axon-growth-regulating RNA-binding protein, to regulate translation in neuronal cytoplasm. Finally, antisense oligos against GI-SINEs perturb sensory neuron outgrowth and nucleolin-ribosome interactions. Thus, a specific subfamily of transposable elements is integral to a physiological circuit linking AP-1 transcription with localized RNA translation.

KW - RNA localization

KW - Short Interspersed Nuclear Elements

KW - axon growth

KW - axonal transport

KW - local translation

KW - nerve injury

KW - neuronal length sensing

KW - non-coding RNA

UR - http://www.scopus.com/inward/record.url?scp=105005190863&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2025.04.030

DO - 10.1016/j.cell.2025.04.030

M3 - مقالة

C2 - 40381624

SN - 0092-8674

JO - Cell

JF - Cell

ER -

Repeat-element RNAs integrate a neuronal growth circuit

Abstract

Keywords

All Science Journal Classification (ASJC) codes

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