TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.

The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.

Gate-Tunable Plasmon-Enhanced Photodetection in a Monolayer MoS2 Phototransistor with Ultrahigh Photoresponsivity.

Monolayer transition metal dichalcogenides (TMDs), direct bandgap materials with an atomically thin nature, are promising materials for electronics and photonics, especially at highly scaled lateral dimensions. However, the characteristically low total absorption of photons in the monolayer TMD has become a challenge in the access to and realization of monolayer TMD-based high-performance optoelectronic functionalities and devices. Here, we demonstrate gate-tunable plasmonic phototransistors (photoFETs) that consist of monolayer molybdenum disulfide (MoS2) photoFETs integrated with the two-dimensional plasmonic crystals. The plasmonic photoFET has an ultrahigh photoresponsivity of 2.7 × 104 AW-1, achieving a 7.2-fold enhancement in the photocurrent compared to pristine photoFETs. This benefits predominately from the combination of the enhancement of the photon-absorption-rate via the strongly localized-electromagnetic-field and the gate-tunable plasmon-induced photocarrier-generation-rate in the monolayer MoS2. These results demonstrate a systematic methodology for designing ultrathin plasmon-enhanced photodetectors based on monolayer TMDs for next-generation ultracompact optoelectronic devices in the trans-Moore era.

Functions and properties of nuclear lncRNAs-from systematically mapping the interactomes of lncRNAs.

Protein and DNA have been considered as the major components of chromatin. But beyond that, an increasing number of studies show that RNA occupies a large amount of chromatin and acts as a regulator of nuclear architecture. A significant fraction of long non-coding RNAs (lncRNAs) prefers to stay in the nucleus and cooperate with protein complexes to modulate epigenetic regulation, phase separation, compartment formation, and nuclear organization. An RNA strand also can invade into double-stranded DNA to form RNA:DNA hybrids (R-loops) in living cells, contributing to the regulation of gene expression and genomic instability. In this review, we discuss how nuclear lncRNAs orchestrate cellular processes through their interactions with proteins and DNA and summarize the recent genome-wide techniques to study the functions of lncRNAs by revealing their interactomes in vivo.

Stereotactic body radiation therapy as an alternative to adrenalectomy for the treatment of pheochromocytomas in 8 dogs.

The objective of this report is to describe the use and outcome of stereotactic body radiation therapy (SBRT) for treatment of pheochromocytomas in 8 dogs. Pheochromocytomas are an uncommon but challenging tumour to manage. Adrenalectomy is the standard of care for treatment of pheochromocytomas in both animals and humans; however, unpredictable catecholamine secretion from the tumour and vascular and local invasion of the tumour and thrombi can pose life-threatening perioperative and anaesthetic risks. SBRT has been investigated as an alternative to adrenalectomy in human patients with pheochromocytomas. Eight dogs with clinical signs, an adrenal mass, and cytology and/or urine normetanephrine/creatinine ratios consistent with pheochromocytoma were treated with SBRT in lieu of adrenalectomy. Three dogs presented with acute hemoabdomen. Seven dogs had caval tumour invasion, 3 with extension into the right atrium. Following SBRT, all dogs had complete resolution of clinical signs and reduced urine normetanephrine/creatinine ratio and/or tumour size. No significant anaesthetic complications were encountered. Acute radiation toxicity was limited to grade I gastrointestinal signs in 3 dogs and resolved within 1-2 days of symptomatic therapy. Five of 8 dogs were alive at the time of follow up, with a median follow up time of 25.8 months. SBRT resulted in a favourable outcome and mitigated the life-threatening risks of adrenalectomy in these 8 dogs. SBRT may be a safe and effective alternative to adrenalectomy for pheochromocytomas in dogs with non-resectable tumours, or for owners averse to the risks of surgery.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

XPF activates break-induced telomere synthesis.

Alternative Lengthening of Telomeres (ALT) utilizes a recombination mechanism and break-induced DNA synthesis to maintain telomere length without telomerase, but it is unclear how cells initiate ALT. TERRA, telomeric repeat-containing RNA, forms RNA:DNA hybrids (R-loops) at ALT telomeres. We show that depleting TERRA using an RNA-targeting Cas9 system reduces ALT-associated PML bodies, telomere clustering, and telomere lengthening. TERRA interactome reveals that TERRA interacts with an extensive subset of DNA repair proteins in ALT cells. One of TERRA interacting proteins, the endonuclease XPF, is highly enriched at ALT telomeres and recruited by telomeric R-loops to induce DNA damage response (DDR) independent of CSB and SLX4, and thus triggers break-induced telomere synthesis and lengthening. The attraction of BRCA1 and RAD51 at telomeres requires XPF in FANCM-deficient cells that accumulate telomeric R-loops. Our results suggest that telomeric R-loops activate DDR via XPF to promote homologous recombination and telomere replication to drive ALT.

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

iDRiP for the systematic discovery of proteins bound directly to noncoding RNA.

More than 90% of the human genome is transcribed into noncoding RNAs, but their functional characterization has lagged behind. A major bottleneck in the understanding of their functions and mechanisms has been a dearth of systematic methods for identifying interacting protein partners. There now exist several methods, including identification of direct RNA interacting proteins (iDRiP), chromatin isolation by RNA purification (ChIRP), and RNA antisense purification, each previously applied towards identifying a proteome for the prototype noncoding RNA, Xist. iDRiP has recently been modified to successfully identify proteomes for two additional noncoding RNAs of interest, TERRA and U1 RNA. Here we describe the modified protocol in detail, highlighting technical differences that facilitate capture of various noncoding RNAs. The protocol can be applied to short and long RNAs in both cultured cells and tissues, and requires ~1 week from start to finish. Here we also perform a comparative analysis between iDRiP and ChIRP. We obtain partially overlapping profiles, but find that iDRiP yields a greater number of specific proteins and fewer mitochondrial contaminants. With an increasing number of essential long noncoding RNAs being described, robust RNA-centric protein capture methods are critical for the probing of noncoding RNA function and mechanism.

Aluminum Plasmonics Enriched Ultraviolet GaN Photodetector with Ultrahigh Responsivity, Detectivity, and Broad Bandwidth.

Plasmonics have been well investigated on photodetectors, particularly in IR and visible regimes. However, for a wide range of ultraviolet (UV) applications, plasmonics remain unavailable mainly because of the constrained optical properties of applicable plasmonic materials in the UV regime. Therefore, an epitaxial single-crystalline aluminum (Al) film, an abundant metal with high plasma frequency and low intrinsic loss is fabricated, on a wide bandgap semiconductive gallium nitride (GaN) to form a UV photodetector. By deliberately designing a periodic nanohole array in this Al film, localized surface plasmon resonance and extraordinary transmission are enabled; hence, the maximum responsivity (670 A W-1) and highest detectivity (1.48 × 1015 cm Hz1/2 W-1) is obtained at the resonance wavelength of 355 nm. In addition, owing to coupling among nanoholes, the bandwidth expands substantially, encompassing the entire UV range. Finally, a Schottky contact is formed between the single-crystalline Al nanohole array and the GaN substrate, resulting in a fast temporal response with a rise time of 51 ms and a fall time of 197 ms. To the best knowledge, the presented detectivity is the highest compared with those of other reported GaN photodetectors.

Perovskite Quantum Dot Lasing in a Gap-Plasmon Nanocavity with Ultralow Threshold.

Lead halide perovskite materials have recently received considerable attention for achieving an economic and tunable laser owing to their solution-processable feature and promising optical properties. However, most reported perovskite-based lasers operate with a large lasing-mode volume, resulting in a high lasing threshold due to the inefficient coupling between the optical gain medium and cavity. Here, we demonstrate a continuous-wave nanolasing from a single lead halide perovskite (CsPbBr3) quantum dot (PQD) in a plasmonic gap-mode nanocavity with an ultralow threshold of 1.9 Wcm-2 under 120 K. The calculated ultrasmall mode volume (∼0.002 λ3) with a z-polarized dipole and the significantly large Purcell enhancement at the corner of the nanocavity inside the gap dramatically enhance the light-matter interaction in the nanocavity, thus facilitating lasing. The demonstration of PQD nanolasing with an ultralow-threshold provides an approach for realizing on-chip electrically driven lasing and integration into on-chip plasmonic circuitry for ultrafast optical communication and quantum information processing.