Global analysis of mRNA isoform half-lives reveals stabilizing and destabilizing elements in yeast.

We measured half-lives of 21,248 mRNA 3' isoforms in yeast by rapidly depleting RNA polymerase II from the nucleus and performing direct RNA sequencing throughout the decay process. Interestingly, half-lives of mRNA isoforms from the same gene, including nearly identical isoforms, often vary widely. Based on clusters of isoforms with different half-lives, we identify hundreds of sequences conferring stabilization or destabilization upon mRNAs terminating downstream. One class of stabilizing element is a polyU sequence that can interact with poly(A) tails, inhibit the association of poly(A)-binding protein, and confer increased stability upon introduction into ectopic transcripts. More generally, destabilizing and stabilizing elements are linked to the propensity of the poly(A) tail to engage in double-stranded structures. Isoforms engineered to fold into 3' stem-loop structures not involving the poly(A) tail exhibit even longer half-lives. We suggest that double-stranded structures at 3' ends are a major determinant of mRNA stability.

"Core-Shell" Wave Function Modulation in Organic Narrowband Emitters.

Efficient red-green-blue primary luminescence with an extraordinarily narrow band and durability is crucial for advanced display applications. Recently, the emergence of multiple-resonance (MR) from short-range atomic interactions has been shown to induce extremely narrow spectral widths in pure organic emitters. However, achieving wide-range color tuning without compromising color purity remains a persistent challenge for MR emitters. Herein, the concept of electronic donor/acceptor "core-shell" modulation is proposed within a boron/nitrogen (B/N) MR skeleton, enabling the rational utilization of intramolecular charge transfer to facilitate wavelength shift. The dense B atoms localized at the center of the molecule effectively compress the electron density and stabilize the lowest unoccupied molecular orbital wave function. This electron-withdrawing core is embedded with peripheral electron-donating atoms. Consequently, doping a single B atom into a deep-blue MR framework led to a profound bathochromic shift from 447 to 624 nm (∼0.8 eV) while maintaining a narrow spectral width of 0.10 eV in this pure-red emitter. Notably, organic light-emitting diodes assisted by thermally activated delayed fluorescence molecules achieved superb electroluminescent stability, with an LT99 (99% of the initial luminance) exceeding 400 h at an initial luminance of 1000 cd m-2, approaching commercial-level performance without the assistance of phosphors.

Expanding Multiple-Resonance Structure of a Double-Borylated Skeleton by Fusing with Indolocarbazole a Multiple-Resonance Donor for Narrowband Green Emission.

Double-borylated multiple-resonance (MR) skeletons are promising templates for high performance, while the chemical design space is relatively limited. Peripheral segments are often used to decorate/fuse MR skeletons and modulate the photophysics but they can also cause unwanted spectral broadening. Herein, a narrowband MR emitter ICzDBA by fusing an MR-featured donor segment indolocarbazole into a double-borylated MR skeleton is developed. In ICzDBA, the nitrogen atom located away from the core benzene ring can also contribute to the generation of the overall MR-featured distribution through the long-range conjugation effect, along with the other boron/nitrogen atoms on the phenyl center. Thus, ICzDBA in toluene displays a narrowband emission peaking at 507 nm with a full width at half maximum of merely 20 nm (0.09 eV). Moreover, organic light-emitting diode devices using ICzDBA emitter exhibit ultrapure green emission with Commission Internationale de l'Eclairage (CIE) coordinates of (0.27, 0.70) and a high external quantum efficiency of 32.5%. These results manifest the importance of MR characters of peripheral decorations/fusions in preserving the narrowband features of MR skeletons, which provides a solution for further expanding MR structures with well-maintained narrowband characters.

High-efficiency stretchable light-emitting polymers from thermally activated delayed fluorescence.

Stretchable light-emitting materials are the key components for realizing skin-like displays and optical biostimulation. All the stretchable emitters reported to date, to the best of our knowledge, have been based on electroluminescent polymers that only harness singlet excitons, limiting their theoretical quantum yield to 25%. Here we present a design concept for imparting stretchability onto electroluminescent polymers that can harness all the excitons through thermally activated delayed fluorescence, thereby reaching a near-unity theoretical quantum yield. We show that our design strategy of inserting flexible, linear units into a polymer backbone can substantially increase the mechanical stretchability without affecting the underlying electroluminescent processes. As a result, our synthesized polymer achieves a stretchability of 125%, with an external quantum efficiency of 10%. Furthermore, we demonstrate a fully stretchable organic light-emitting diode, confirming that the proposed stretchable thermally activated delayed fluorescence polymers provide a path towards simultaneously achieving desirable electroluminescent and mechanical characteristics, including high efficiency, brightness, switching speed and stretchability as well as low driving voltage.

Juvenile hormone inhibits adult cuticle formation in Drosophila melanogaster through Kr-h1/Dnmt2-mediated DNA methylation of Acp65A promoter.

Differentiation of imaginal epidermal cells of Drosophila melanogaster to form adult cuticles occurs at approximately 40-93 h after puparium formation. Juvenile hormone (JH) given at pupariation results in formation of a second pupal cuticle in the abdomen instead of the adult cuticle. Although the adult cuticle gene Acp65A has been reported to be down-regulated following JH treatment, the regulatory mechanism remains unclear. Here, we found that the JH primary response gene Krüppel homologue 1 (Kr-h1) plays a vital role in the repression of adult cuticle formation through the mediation of JH action. Overexpression of Kr-h1 mimicked-while knocking down of Kr-h1 attenuated-the inhibitory action of JH on the formation of the adult abdominal cuticle. Further, we found that Kr-h1 inhibited the transcription of Acp65A by directly binding to the consensus Kr-h1 binding site (KBS) within the Acp65A promoter region. Moreover, the DNA methyltransferase Dnmt2 was shown to interact with Kr-h1, combined with the KBS to promote the DNA methylation of sequences around the KBS, in turn inhibiting the transcription of Acp65A. This study advances our understanding of the molecular basis of the "status quo" action of JH on the Drosophila adult metamorphosis.

A Quadruple-Borylated Multiple-Resonance Emitter with para/meta Heteroatomic Patterns for Narrowband Orange-Red Emission.

Hindered by spectral broadening issues with redshifted emission, long-wavelength (e.g., maxima beyond 570 nm) multiple resonance (MR) emitters with full width at half maxima (FWHMs) below 20 nm remain absent. Herein, by strategically embedding diverse boron (B)/nitrogen (N) atomic pairs into a polycyclic aromatic hydrocarbon (PAH) skeleton, we propose a hybrid pattern for the construction of a long-wavelength narrowband MR emitter. The proof-of-concept emitter B4N6-Me realized orange-red emission with an extremely small FWHM of 19 nm (energy unit: 70 meV), representing the narrowest FWHM among all reported long-wavelength MR emitters. Theoretical calculations revealed that the cooperation of the applied para B-π-N and para B-π-B/N-π-N patterns is complementary, which gives rise to both narrowband and redshift characteristics. The corresponding organic light-emitting diode (OLED) employing B4N6-Me achieved state-of-the-art performance, e.g., a narrowband orange-red emission with an FWHM of 27 nm (energy unit: 99 meV), an excellent maximum external quantum efficiency (EQE) of 35.8 %, and ultralow efficiency roll-off (EQE of 28.4 % at 1000 cd m-2 ). This work provides new insights into the further molecular design and synthesis of long-wavelength MR emitters.

Combining Carbazole Building Blocks and ν-DABNA Heteroatom Alignment for a Double Boron-Embedded MR-TADF Emitter with Improved Performance.

Building blocks and heteroatom alignments are two determining factors in designing multiple resonance (MR)-type thermally activated delayed fluorescence (TADF) emitters. Carbazole-fused MR emitters, represented by CzBN derivatives, and the heteroatom alignments of ν-DABNA are two star series of MR-TADF emitters that show impressive performances from the aspects of building blocks and heteroatom alignments, respectively. Herein, a novel CzBN analog, Π-CzBN, featuring ν-DABNA heteroatom alignment is developed via facile one-shot lithium-free borylation. Π-CzBN exhibits superior photophysical properties with a photoluminescence quantum yield close to 100 % and narrowband sky blue emission with a full width at half maximum (FWHM) of 16 nm/85 meV. It also gives efficient TADF properties with a small singlet-triplet energy offset of 40 meV and a fast reverse intersystem crossing rate of 2.9×105  s-1 . The optimized OLED using Π-CzBN as the emitter achieves an exceptional external quantum efficiency of 39.3 % with a low efficiency roll-off of 20 % at 1000 cd m-2 and a narrowband emission at 495 nm with FWHM of 21 nm/106 meV, making it one of the best reported devices based on MR emitters with comprehensive performance.

A Highly Twisted Carbazole-Fused DABNA Derivative as an Orange-Red TADF Emitter for OLEDs with Nearly 40 % EQE.

Multiple resonance (MR) type thermally activated delayed fluorescence (TADF) material is currently a research hotspot in organic light-emitting diodes (OLEDs) due to their high color purity and high exciton utilization. However, there are only a handful of MR-TADF emitters with emissions beyond the blue-to-green region. The very limited emission colors for MR-TADF emitters are mainly caused by the fact that so far molecular modifications of MR-TADF do not offer much change in the emission colors. Here, we report a new approach to modifying a prototypical MR core of DABNA by fusing carbazoles to the MR framework. The carbazole-fused molecule (TCZ-F-DABNA) basically maintains the MR-dominated features of DABNA while red-shifting the emission. Its OLED achieves an external quantum efficiency of 39.2 % with a peak at 588 nm, which is a record-high efficiency for OLEDs with peaks beyond 560 nm. This work provides a new approach for significantly tunning emission colors of MR-TADF emitters.

Managing Locally Excited and Charge-Transfer Triplet States to Facilitate Up-Conversion in Red TADF Emitters That Are Available for Both Vacuum- and Solution-Processes.

Developing red thermally activated delayed fluorescence (TADF) emitters for high-performance OLEDs is still facing great challenge. Herein, three red TADF emitters, pDBBPZ-DPXZ, pDTBPZ-DPXZ, and oDTBPZ-DPXZ, are designed and synthesized with same donor-acceptor (D-A) backbone with different peripheral groups attaching on the A moieties. Their lowest triplet states change from locally excited to charge transfer character leading to significantly enhance reverse intersystem crossing process. In particular, oDTBPZ-DPXZ exhibits efficient TADF feature and exciton utilization. It not only achieves an external quantum efficiency (EQE) of 20.1 % in red vacuum-processed OLED, but also realize a high EQE of 18.5 % in a solution-processed OLED, which is among the best results in solution-processed red TADF OLEDs. This work provides an effective strategy for designing red TADF molecules by managing energy level alignments to facilitate the up-conversion process and thus enhance exciton harvesting.

Characterizing the Conformational Distribution in an Amorphous Film of an Organic Emitter and Its Application in a "Self-Doping" Organic Light-Emitting Diode.

The conformational distribution and mutual interconversion of thermally activated delayed fluorescence (TADF) emitters significantly affect the exciton utilization. However, their influence on the photophysics in amorphous film states is still not known due to the lack of a suitable quantitative analysis method. Herein, we used temperature-dependent time-resolved photoluminescence spectroscopy to quantitatively measure the relative populations of the conformations of a TADF emitter for the first time. We further propose a new concept of "self-doping" for realizing high-efficiency nondoped OLEDs. Interestingly, this "compositionally" pure film actually behaves as a film with a dopant (quasi-equatorial form) in a matrix (quasi-axial form). The concentration-induced quenching that may occur at high concentrations is thus expected to be effectively relieved. The "self-doping" OLED prepared with the newly developed TADF emitter TP2P-PXZ as a neat emitting layer realizes a high maximum external quantum efficiency of 25.4 % and neglectable efficiency roll-off.

Species-specific factors mediate extensive heterogeneity of mRNA 3' ends in yeasts.

Most eukaryotic genes express mRNAs with alternative polyadenylation sites at their 3' ends. Here we show that polyadenylated 3' termini in three yeast species (Saccharomyces cerevisiae, Kluyveromyces lactis, and Debaryomyces hansenii) are remarkably heterogeneous. Instead of a few discrete 3' ends, the average yeast gene has an "end zone," a >200 bp window with >60 distinct poly(A) sites, the most used of which represents only 20% of the mRNA molecules. The pattern of polyadenylation within this zone varies across species, with D. hansenii possessing a higher focus on a single dominant point closer to the ORF terminus. Some polyadenylation occurs within mRNA coding regions with a strong bias toward the promoter. The polyadenylation pattern is determined by a highly degenerate sequence over a broad region and by a local sequence that relies on A residues after the cleavage point. Many dominant poly(A) sites are predicted to adopt a common secondary structure that may be recognized by the cleavage/polyadenylation machinery. We suggest that the end zone reflects a region permissive for polyadenylation, within which cleavage occurs preferentially at the A-rich sequence. In S. cerevisiae strains, D. hansenii genes adopt the S. cerevisiae polyadenylation profile, indicating that the polyadenylation pattern is mediated primarily by species-specific factors.

A nuclear receptor-like pathway regulating multidrug resistance in fungi.

Multidrug resistance (MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc-cluster transcription-factor family (for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/MED15 subunit of the Mediator co-activator and its activator-targeted KIX domain in antifungal/xenobiotic-dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor-like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug-resistant fungal infections.

Efficient, narrow-band, and stable electroluminescence from organoboron-nitrogen-carbonyl emitter.

Organic light-emitting diodes (OLEDs) exploiting simple binary emissive layers (EMLs) blending only emitters and hosts have natural advantages in low-cost commercialization. However, previously reported OLEDs based on binary EMLs hardly simultaneously achieved desired comprehensive performances, e.g., high efficiency, low efficiency roll-off, narrow emission bands, and high operation stability. Here, we report a molecular-design strategy. Such a strategy leads to a fast reverse intersystem crossing rate in our designed emitter h-BNCO-1 of 1.79×105 s-1. An OLED exploiting a binary EML with h-BNCO-1 achieves ultrapure emission, a maximum external quantum efficiency of over 40% and a mild roll-off of 14% at 1000 cd·m-2. Moreover, h-BNCO-1 also exhibits promising operational stability in an alternative OLED exploiting a compact binary EML (the lifetime reaching 95% of the initial luminance at 1000 cd m-2 is ~ 137 h). Here, our work has thus provided a molecular-design strategy for OLEDs with promising comprehensive performance.

Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3'-end formation.

Genome-wide mapping of nucleosomes generated by micrococcal nuclease (MNase) suggests that yeast promoter and terminator regions are very depleted of nucleosomes, predominantly because their DNA sequences intrinsically disfavor nucleosome formation. However, MNase has strong DNA sequence specificity that favors cleavage at promoters and terminators and accounts for some of the correlation between occupancy patterns of nucleosomes assembled in vivo and in vitro. Using an improved method for measuring nucleosome occupancy in vivo that does not involve MNase, we confirm that promoter regions are strongly depleted of nucleosomes, but find that terminator regions are much less depleted than expected. Unlike at promoter regions, nucleosome occupancy at terminators is strongly correlated with the orientation of and distance to adjacent genes. In addition, nucleosome occupancy at terminators is strongly affected by growth conditions, indicating that it is not primarily determined by intrinsic histone-DNA interactions. Rapid removal of RNA polymerase II (pol II) causes increased nucleosome occupancy at terminators, strongly suggesting a transcription-based mechanism of nucleosome depletion. However, the distinct behavior of terminator regions and their corresponding coding regions suggests that nucleosome depletion at terminators is not simply associated with passage of pol II, but rather involves a distinct mechanism linked to 3'-end formation.

RGB Thermally Activated Delayed Fluorescence Emitters for Organic Light-Emitting Diodes toward Realizing the BT.2020 Standard.

With the surging demand for ultra-high-resolution displays, the International Telecommunication Union (ITU) announce the next-generation color gamut standard, named ITU-R Recommendation BT.2020, which not only sets a seductive but challenging milestone for display technologies but also urges researchers to recognize the importance of color coordinates. Organic light-emitting diodes (OLEDs) are an important display technology in current daily life, but they face challenges in approaching the BT.2020 standard. Thermally activated delayed fluorescence (TADF) emitters have bright prospects in OLEDs because they possess 100% theoretical exciton utilization. Thus, the development of TADF emitters emitting primary red (R), green (R), and blue (B) emission is of great significance. Here, a comprehensive overview of the latest advancements in TADF emitters that exhibit Commission Internationale de l'Éclairage (CIE) coordinates surpassing the National Television System Committee (NTSC) and approaching BT.2020 standards is presented. Rational strategies for molecular designs, as well as the resulting photophysical properties and OLED performances, are discussed to elucidate the underlying mechanisms for shifting the CIE coordinates of both donor-acceptor and multiple resonance (MR) typed TADF emitters toward the BT.2020 standard. Finally, the challenges in realization of the wide-color-gamut BT.2020 standard and the prospects for this research area are provided.

Juvenile hormone suppresses sensory organ precursor determination to block Drosophila adult abdomen morphogenesis.

Juvenile hormone (JH) has a classic "status quo" action at both the pupal and adult molts when administrated exogenously. In Drosophila, treatment with JH at pupariation inhibits the formation of abdominal bristles, which are derived from the histoblasts. However, the mechanism via which JH exerts this effect remains poorly understood. In this study, we analyzed the effect of JH on histoblast proliferation, migration, and differentiation. Our results indicated that whereas the proliferation and migration of histoblasts remained unaffected following treatment with a JH mimic (JHM), their differentiation, particularly the specification of sensor organ precursor (SOP) cells, was inhibited. This effect was attributable to downregulated proneural genes achaete (ac) and Scute (sc) expression levels, which prevented the specification of SOP cells in proneural clusters. Moreover, Kr-h1 was found to mediate this effect of JHM. Histoblast-specific overexpression or knockdown of Kr-h1, respectively mimicked or attenuated the effects exerted by JHM on abdominal bristle formation, SOP determination, and transcriptional regulation of ac and sc. These results indicated that the defective SOP determination was responsible for the inhibition of abdominal bristle formation by JHM, which, in turn, was mainly mediated via the transducing action of Kr-h1.

A TADF Emitter with Dual Para-Positioned Donors Enables OLEDs with Improved Efficiency and CIE Coordinates Close to the Rec. 2020 Red Standard.

Developing red thermally activated delayed fluorescence (TADF) emitters concurrently with high efficiency and emission color close to the BT.2020 red standard is an ongoing challenge. Herein, we developed a new red TADF emitter BCN-TPA, in which two identical donors are attached at the para-positions of one fused phenyl ring in the acceptor framework. Such an arrangement mode can lead the donors with an obvious superimposed effect comparing the conventional arrangement with edge-capped donors on the acceptor. Thus, BCN-TPA yields enhanced overall donor strength with numerous superiorities, such as high oscillator strength and narrow singlet-triplet energy difference, thus giving rise to red-shifted emission with improved overall exciton utilization. In an organic light-emitting diode, BCN-TPA presents efficient deep-red electroluminescence with a maximum external quantum efficiency of 27.6% and a peak at 656 nm, corresponding to CIE coordinates of (0.686, 0.304), which are very close to the red primary in the BT.2020 standard. To the best of our knowledge, this is one of the topmost efficiencies in the field of deep-red TADF OLEDs. This work exemplifies an easy design principle for constructing high-performance deep-red TADF emitters, providing unique molecular-level insights toward improving color quality and elevating efficiency based on conventional D-A type molecular frameworks.

Integrating the atomically separated frontier molecular orbital distribution of two multiple resonance frameworks through a single bond for high-efficiency narrowband emission.

Atomically separated frontier molecular orbital (FMO) distribution plays a crucial role in achieving narrowband emissions for multiple resonance (MR)-type thermally activated delayed fluorescence emitters. Directly peripherally decorating a MR framework with donor or acceptor groups is a common strategy for developing MR emitters. However, this approach always induces bonding features and thus spectral broadening as a side effect. How direct donor/acceptor decoration enhances atomic FMO separation while avoiding bonding features has not been explored. For this aim, two MR derivatives are synthesized by integrating two MR frameworks at different sites. Following resonance alignment, DOBNA-m-CzBN avoids breaking nonbonding FMO features at the single connecting bond and shows enhanced MR characteristics, with a sharp emission at 491 nm and a full width at half maximum (FWHM) of 24 nm/118 meV. Conversely, DOBNA-p-CzBN emerges as a bonding feature due to its continuous π-conjugation extension, with a broadened FWHM of 26 nm/132 meV peaking at 497 nm. Impressively, both emitters exhibit outstanding external quantum efficiencies of 37.8-38.6% in organic light-emitting diodes (OLEDs), demonstrating improved performance with rigid acceptor decoration. Distinctly, the electroluminescence of DOBNA-m-CzBN shows a narrower FWHM than that of DOBNA-p-CzBN. This work for the first time reports the enhancement of atomic FMO separation for MR emitters via peripheral decoration through a single bond and provides a more comprehensive illustration for further development of MR emitters.

Regiochemistry of Donor Dendrons Controls the Performance of Thermally Activated Delayed Fluorescence Dendrimer Emitters for High Efficiency Solution-Processed Organic Light-Emitting Diodes.

The potential of dendrimers exhibiting thermally activated delayed fluorescence (TADF) as emitters in solution-processed organic light-emitting diodes (OLEDs) has to date not yet been realized. This in part is due to a poor understanding of the structure-property relationship in dendrimers where reports of detailed photophysical characterization and mechanism studies are lacking. In this report, using absorption and solvatochromic photoluminescence studies in solution, the origin and character of the lowest excited electronic states in dendrimers with multiple dendritic electron-donating moieties connected to a central electron-withdrawing core via a para- or a meta-phenylene bridge is probed. Characterization of host-free OLEDs reveals the superiority of meta-linked dendrimers as compared to the already reported para-analogue. Comparative temperature-dependent time-resolved solid-state photoluminescence measurements and quantum chemical studies explore the effect of the substitution mode on the TADF properties and the reverse intersystem crossing (RISC) mechanism, respectively. For TADF dendrimers with similarly small ∆EST , it is observed that RISC can be enhanced by the regiochemistry of the donor dendrons due to control of the reorganization energies, which is a heretofore unexploited strategy that is distinct from the involvement of intermediate triplet states through a nonadiabatic (vibronic) coupling with the lowest singlet charge transfer state.