On the functional relevance of spatiotemporally-specific patterns of experience-dependent long noncoding RNA expression in the brain

Liau, Wei-Siang; Samaddar, Sarbani; Banerjee, Sourav; Bredy, Timothy W.

doi:10.1080/15476286.2020.1868165

Cited by 21 publications

(13 citation statements)

References 221 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may influence how it participates in behavioural responses to stress (Kucharski et al, 2020) and as an architect of chromatin modification supporting age-related spatial memory processes (Butler et al, 2019). It is increasingly becoming evident that there are many factors beyond transcriptional abundance that determine whether a lncRNA is functionally relevant (Liau et al, 2021). We therefore decided to look more deeply into how lncRNAs are regulated in the ILPFC, and how they are functionally activated in response to fear extinction learning.…”

Section: Resultsmentioning

confidence: 99%

“…LncRNAs, defined as any RNA longer than 200nt and without protein coding potential, are expressed in a highly cell-type and spatiotemporally specific manner in the adult brain (Mercer et al, 2008), with 40% of all lncRNAs identified to date shown to be enriched in neurons. It has therefore been proposed that lncRNAs are uniquely positioned to mediate rapid responses to environmental stimuli and to promote cognition (Spadaro and Bredy, 2012;Liau et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

Zhao

Wang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Long-noncoding RNA (lncRNA) comprise a new class of genes that have been assigned key roles in development and disease. Many lncRNAs are specifically transcribed in the brain where they regulate the expression of protein-coding genes that underpin neuronal function; however, their role in learning and memory remains largely unexplored. We used RNA Capture-Seq to identify a large population of lncRNAs that are expressed in the infralimbic cortex of adult male mice in response to fear-related learning, with 14.5% of these annotated in the GENCODE database as lncRNAs with no known function. We combined these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear-extinction learning, and revealed 434 lncRNAs derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discovered an experience-induced lncRNA called ADRAM that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate early gene Nr4a2. This leads to the expulsion of histone deactylases 3 and 4, and the recruitment of the histone acetyltransferase creb binding protein, which drives learning-induced Nr4a2 expression. Knockdown of ADRAM disrupts this interaction, blocks the expression of Nr4a2, and ultimately impairs the formation of fear-extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain, highlights enhancer-derived RNAs (eRNAs) as key players in the epigenetic regulation of gene expression associated with fear extinction, and suggests eRNAs, such as ADRAM, may constitute viable targets in developing novel treatments for fear-related anxiety disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

Zhao

Wang

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In all these cases showcasing examples of direct interaction between lncRNAs and proteins, only few direct examples of extranuclear interactions of lncRNAs and proteins are found. It is tantalizing to speculate that some lncRNAs might be implicated in the direct regulation of phase separation and condensate formation at the synapse [ 154 ], in a similar manner to what has been observed in the nucleus [ 155 ], although direct proof is still missing. The most relevant lncRNAs acting in the brain and in neurons are summarized in Table 1 .…”

Section: Functional Classification Of Neuronal Lncrnasmentioning

confidence: 99%

Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

2021

View full text Add to dashboard Cite

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

show abstract

“…Recent studies have also begun to shed light on the expression, regulation and function of lncRNAs in neurons [11][12][13]. A review article by Tim Bredy and colleagues illuminates the subcellular expression and synaptic functions of lncRNAs [14]. By modulating transcription in the nucleus, mediating mRNA stability and associating with RNA binding proteins in the cytoplasm, lncRNA proves itself a major regulator of neuronal functions.…”

Section: Editorialmentioning

confidence: 99%

The emerging RNA-centric world of neurobiology

Puthanveettil

2021

RNA Biology

View full text Add to dashboard Cite

On the functional relevance of spatiotemporally-specific patterns of experience-dependent long noncoding RNA expression in the brain

Cited by 21 publications

References 221 publications

On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

On the discovery of ADRAM, an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

The emerging RNA-centric world of neurobiology

Contact Info

Product

Resources

About