Regulation of axon regeneration by the RNA repair and splicing pathway

Song, Yuanquan; Sretavan, David W.; Salegio, Ernesto A.; Berg, Jim; Huang, Xi; Cheng, Tong; Xiong, Xin; Meltzer, Shan; Han, Chun; Nguyen, Trong-Tuong; Bresnahan, Jacqueline C.; Beattie, Michael S.; Jan, Yuh Nung

doi:10.1038/nn.4019

Cited by 54 publications

(81 citation statements)

References 55 publications

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“…The RNA processing enzymes RNA 3´-terminal phosphate cyclases (RTCA and RTCB) act to inhibit axon regeneration after nerve injury in C. elegans and D. melanogaster 88,89 . By contrast, protein archease, an RNA ligase cofactor that functions downstream of RTCA, serves as a pro-regeneration factor 89 . These RNA processing enzymes are involved in the unconventional mRNA splicing of X-box-binding protein 1 (XBP1), a stress sensor involved in the .…”

Section: Injury Signallingmentioning

confidence: 99%

“…These RNA processing enzymes are involved in the unconventional mRNA splicing of X-box-binding protein 1 (XBP1), a stress sensor involved in the . XBP1 is required for regeneration and appears to have a role that is conserved in C. elegans, D. melanogaster and mice 89–91 . Another type of stress response, involving glucocorticoid release and increased expression of glucocorticoid receptors in sensory neurons, is also integral to the regenerative response after nerve injury 71 .…”

Section: Injury Signallingmentioning

confidence: 99%

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Intrinsic mechanisms of neuronal axon regeneration

2018

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Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs. Although many questions remain about the interplay between these mechanisms, these new findings provide important insights into the pivotal role of coordinated gene expression and chromatin remodelling in the neuronal response to injury.

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Section: Injury Signallingmentioning

confidence: 99%

Section: Injury Signallingmentioning

confidence: 99%

Intrinsic mechanisms of neuronal axon regeneration

2018

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“…Loss of function in rtcb-1 enhances motor neuron regeneration, independent of known catalytic roles of RtcB in ligation of tRNAs or splicing of the mRNA for the unfolded protein response sensor xbp-1. Conversely, the RNA cyclase RtcA has been shown to repress regeneration in Drosophila and mammalian neurons (Song et al 2015). In Drosophila, this effect was interpreted as involving canonical RtcA functions in xbp-1 splicing.…”

Section: Rna Processing and Regenerationmentioning

confidence: 99%

“…In Drosophila, this effect was interpreted as involving canonical RtcA functions in xbp-1 splicing. xbp-1 itself is required for efficient axon regeneration in C. elegans and in Drosophila (Nix et al 2014;Song et al 2015). RtcA and RtcB catalyze opposing reactions, so it is less evident why loss of function in either gene should have the same regeneration-enhancing effect.…”

Section: Rna Processing and Regenerationmentioning

confidence: 99%

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Chisholm¹,

Hutter

Jin

et al. 2016

Genetics

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The correct wiring of neuronal circuits depends on outgrowth and guidance of neuronal processes during development. In the past two decades, great progress has been made in understanding the molecular basis of axon outgrowth and guidance. Genetic analysis in Caenorhabditis elegans has played a key role in elucidating conserved pathways regulating axon guidance, including Netrin signaling, the slit Slit/Robo pathway, Wnt signaling, and others. Axon guidance factors were first identified by screens for mutations affecting animal behavior, and by direct visual screens for axon guidance defects. Genetic analysis of these pathways has revealed the complex and combinatorial nature of guidance cues, and has delineated how cues guide growth cones via receptor activity and cytoskeletal rearrangement. Several axon guidance pathways also affect directed migrations of non-neuronal cells in C. elegans, with implications for normal and pathological cell migrations in situations such as tumor metastasis. The small number of neurons and highly stereotyped axonal architecture of the C. elegans nervous system allow analysis of axon guidance at the level of single identified axons, and permit in vivo tests of prevailing models of axon guidance. C. elegans axons also have a robust capacity to undergo regenerative regrowth after precise laser injury (axotomy). Although such axon regrowth shares some similarities with developmental axon outgrowth, screens for regrowth mutants have revealed regenerationspecific pathways and factors that were not identified in developmental screens. Several areas remain poorly understood, including how major axon tracts are formed in the embryo, and the function of axon regeneration in the natural environment. KEYWORDS netrin; semaphorin; ephrin; Wnt; Slit; Robo; fasciculation; DLK; growth cone; actin; microtubule; WormBook

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“…This "epilogue" was extended very recently by the publication of data on a possible role of the rtcAB operon in E. coli in RNA repair and the maintenance of ribosome homeostasis (58,59) and, in one specific case, in the re-ligation by RtcB of 16S rRNA cleaved by a stress-induced endoribonuclease (59). Equally inspiring are recent findings implicating cyclase/RtcA in neuronal functions in metazoa, in association with either RNA transport in mouse neurites (60) or the regulation of axon regeneration in Drosophila and rodent neurons (61). Clearly, we abandoned research on cyclase 20 years too soon!…”

Section: Chasing Functions Of the Rna 3-phosphate Cyclase And Other Rmentioning

confidence: 99%

Traversing the RNA world

Filipowicz

2017

Journal of Biological Chemistry

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An invitation to write a "Reflections" type of article creates a certain ambivalence: it is a great honor, but it also infers the end of your professional career. Before you vanish for good, your colleagues look forward to an interesting but entertaining account of the ups-and-downs of your past research and your views on science in general, peppered with indiscrete anecdotes about your former competitors and collaborators. What follows will disappoint those who await complaint and criticism, for example, about the difficulties of doing research in the 1960s and 1970s in Eastern Europe, or those seeking very personal revelations. My scientific life has in fact seen many happy coincidences, much good fortune, and several lucky escapes from situations that at the time were quite scary. I have also been fortunate with regard to competitors and collaborators, particularly because, whenever possible, I tried to "neutralize" my rivals by collaborating with them -to the benefit of all. I recommend this strategy to young researchers to dispel the nightmares that can occur when competing against powerful contenders. I have been blessed with the selection of my research topic: RNA biology. Over the last five decades, new and unexpected RNA-related phenomena emerged almost yearly. I experienced them very personally while studying transcription, translation, RNA splicing, ribosome biogenesis, and more recently, different classes of regulatory non-coding RNAs, including microRNAs. Some selected research and para-research stories, also covering many wonderful people I had a privilege to work with, are summarized below.My mother told me that I was born with a caul (in Polish, w czepku urodzony, which literally means "born in a bonnet"). This is traditionally the sign of a person who will always enjoy good luck. I am not sure that it turned out that way for others with this rare birth phenomenon, e.g. Lord Byron, Charlemagne, Sigmund Freud, and Napoleon, but my survival as a one-year-old of the 1944 Warsaw Uprising and the ensuing destruction of the city by German troops does nothing to destroy the hypothesis. My parents were actually very courageous to conceive me in that hell, where my father served in the underground army (Armia Krajowa) controlled by the Londonbased Polish government-in-exile. In 1946, with Warsaw destroyed, my family moved to the industrial city of Lodz, and my father became involved in setting up a Department of General and Physiological Chemistry at the newly formed Medical University of Lodz. He became its chairman in the early 1950s.Given my father's position, I was exposed to biology and chemistry since my early childhood, and this greatly influenced my professional future. Our rather spacious apartment served as an extension of his laboratory and was usually full of mice. The poor animals were often not so attractive given that part of his research concerned vitamin deficiencies. Laying the white mice out on our black grand piano as a backdrop for photographic documentation didn't necessarily improve...

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Regulation of axon regeneration by the RNA repair and splicing pathway

Cited by 54 publications

References 55 publications

Intrinsic mechanisms of neuronal axon regeneration

Intrinsic mechanisms of neuronal axon regeneration

The Genetics of Axon Guidance and Axon Regeneration in Caenorhabditis elegans

Traversing the RNA world

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