The DEAH-box helicase DHX36 mediates dendritic localization of the neuronal precursor-microRNA-134

Bicker, Silvia; Khudayberdiev, Sharof; Weiß, Kerstin; Zocher, Kathleen; Baumeister, Stefan; Schratt, Gerhard

doi:10.1101/gad.211243.112

Cited by 111 publications

(135 citation statements)

References 32 publications

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“…RHAU has been shown to specifically bind several non-quadruplex RNAs (1,25); however, this is the first time it has been shown to have affinity for adenosine-rich single-stranded RNA. Whether this affinity is specific to the adenosine-rich stretch of BC200 or RHAU binds a broad spectrum of RNAs containing similar repetitive elements remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

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RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3′-Tail of the Long Non-coding RNA BC200 (BCYRN1)

Booy¹,

McRae²,

Howard³

et al. 2016

Journal of Biological Chemistry

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RNA helicase associated with AU-rich element (RHAU) is an ATP-dependent RNA helicase that demonstrates high affinity for quadruplex structures in DNA and RNA. To elucidate the significance of these quadruplex-RHAU interactions, we have performed RNA co-immunoprecipitation screens to identify novel RNAs bound to RHAU and characterize their function. In the course of this study, we have identified the non-coding RNA BC200 (BCYRN1) as specifically enriched upon RHAU immunoprecipitation. Although BC200 does not adopt a quadruplex structure and does not bind the quadruplex-interacting motif of RHAU, it has direct affinity for RHAU in vitro. Specifically designed BC200 truncations and RNase footprinting assays demonstrate that RHAU binds to an adenosine-rich region near the 3-end of the RNA. RHAU truncations support binding that is dependent upon a region within the C terminus and is specific to RHAU isoform 1. Tests performed to assess whether BC200 interferes with RHAU helicase activity have demonstrated the ability of BC200 to act as an acceptor of unwound quadruplexes via a cytosine-rich region near the 3-end of the RNA. Furthermore, an interaction between BC200 and the quadruplex-containing telomerase RNA was confirmed by pull-down assays of the endogenous RNAs. This leads to the possibility that RHAU may direct BC200 to bind and exert regulatory functions at quadruplex-containing RNA or DNA sequences.RNA helicase associated with AU-rich element (RHAU), 8 also known as DHX36 and G4R1, is an ATP-dependent DEAHbox RNA helicase initially characterized as a regulator of mRNA stability via binding to the AU-rich element of urokinase plasminogen activator mRNA (1). Subsequent to this, the discovery that RHAU possesses the ability to unwind both DNA and RNA quadruplexes shifted the focus of RHAU to a role in quadruplex biology (2-4).Quadruplexes are stable secondary structures that occur in guanine-rich nucleic acids through the alignment and hydrogen bonding of guanines in multiple tetrad planes (5). A typical requirement for quadruplex formation is the presence of four tracts of three or more guanines that align in parallel or antiparallel strands with short (Ͻ7-nt) interspersed loops (6); however, quadruplexes with longer loops have also been reported (7,8). Quadruplexes have been shown to possess myriad roles in gene transcription and post-transcriptional regulation of both coding and non-coding RNAs (9 -16).The quadruplex binding specificity of RHAU is mediated by a short N-terminal motif, referred to as the RHAU-specific motif (RSM). In addition to the RSM, RHAU contains a catalytic helicase core (DEXDc and HELICc domains) as well as an HA2 domain and oligosaccharide binding (OB) fold. Whereas the RSM confers quadruplex interacting specificity, maximal quadruplex binding affinity requires the presence of the helicase core (17, 18). The DHX36 gene generates two known splice variants of RHAU. Whereas isoform 1 localizes to both nucleus and cytoplasm, isoform 2 lacks 14 amino acids within the helicase domain and is p...

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Section: Discussionmentioning

confidence: 99%

“…RHAU has also garnered attention for complicity with several non-coding RNAs, both in the regulation of subcellular localization of specific microRNAs and in the remodeling of quadruplexes within the 5Ј-region of the telomerase RNA (22)(23)(24)(25). Furthermore, RHAU has been related to critical roles in development, differentiation, and immunity (26 -29).…”

mentioning

confidence: 99%

RNA Helicase Associated with AU-rich Element (RHAU/DHX36) Interacts with the 3′-Tail of the Long Non-coding RNA BC200 (BCYRN1)

Booy¹,

McRae²,

Howard³

et al. 2016

Journal of Biological Chemistry

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“…The identity of this repressor molecule and whether it is subjected to activity regulation in neurons is, however, unknown [31]. Moreover, it was recently shown that the DEAH-box protein DHX36, which mediates the transport of pre-miR-134 to dendrites, protects the pre-miR-134 from Dicer processing by binding to the terminal loop structure [32] (figure 1c, right panel). As reported in §1, AGO proteins also participate in miRNA biogenesis, but evidence about this aspect of AGO function in neurons has still not been provided.…”

Section: Regulation Of Mirnas By Neuronal Activity (A) Activity-depenmentioning

confidence: 99%

MicroRNAs and synaptic plasticity—a mutual relationship

Aksoy‐Aksel

Zampa

Schratt

2014

Phil. Trans. R. Soc. B

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109

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MicroRNAs (miRNAs) are rapidly emerging as central regulators of gene expression in the postnatal mammalian brain. Initial studies mostly focused on the function of specific miRNAs during the development of neuronal connectivity in culture, using classical gain-and loss-of-function approaches. More recently, first examples have documented important roles of miRNAs in plastic processes in intact neural circuits in the rodent brain related to higher cognitive abilities and neuropsychiatric disease. At the same time, evidence is accumulating that miRNA function itself is subjected to sophisticated control mechanisms engaged by the activity of neural circuits. In this review, we attempt to pay tribute to this mutual relationship between miRNAs and synaptic plasticity. In particular, in the first part, we summarize how neuronal activity influences each step in the lifetime of miRNAs, including the regulation of transcription, maturation, gene regulatory function and turnover in mammals. In the second part, we discuss recent examples of miRNA function in synaptic plasticity in rodent models and their implications for higher cognitive function and neurological disorders, with a special emphasis on epilepsy as a disorder of abnormal nerve cell activity.

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“…A major advance in the field is a recent study that provided insight into the transport and sorting of pre-miR-134, the precursor form of miR-134, in dendrites of hippocampal neurons (Bicker et al, 2013).…”

Section: The Mainstream: Mirnasmentioning

confidence: 99%