A slow dynamic RNA switch regulates processing of microRNA-21

The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of a majority of eukaryotic genes, and whose dysregulation is a driver of many human diseases. Here we report the discovery of a very slow (0.1 sec) conformational rearrangement at the Dicer cleavage site of pre-miR-21 which regulates the relative concentration of readily processed and inefficiently processed structural states. We show this dynamic switch is affected by single nucleotide mutations and can be biased by small molecule and peptide ligands, which can direct the microRNA to occupy the inefficiently processed state and reduce processing efficiency. This result reveals a new mechanism of RNA regulation and suggests a chemical approach to suppressing or activating pathogenic microRNAs by selective stabilization of the unprocessed or processed state.

LOS PROCESOS DE ESTABILIZACIÓN DE EMPLEO TEMPORAL EN EL REAL DECRETO-LEY 14/2021, DE 6 DE JULIO, DE MEDIDAS URGENTES PARA LA REDUCCIÓN DE LA TEMPORALIDAD EN EL EMPLEO

El art. 2 del Real Decreto-ley 14/2021, de 6 de julio, de medidas urgentes para la reducción de la temporalidad en el empleo público, prevé nuevos procesos de estabilización de empleo temporal para atajar la excesiva temporalidad en las Administraciones Públicas y cumplir con las indicaciones de la Unión Europea a nuestro país en este sentido. En el presente artículo se estudia el régimen jurídico aplicable a estos procesos de estabilización de empleo temporal y muy en particular la compensación económica que se reconoce en favor del personal funcionario interino o el personal laboral temporal afectado por los procesos de estabilización de empleo temporal que, estando en activo como tal y habiendo participado en el proceso selectivo de estabilización, viera finalizada su relación con la Administración por la no superación del proceso selectivo, el carácter potestativo u obligatorio de los procesos de estabilización de empleo temporal, los sistemas selectivos, la valoración de los méritos, las pruebas y las notas de corte. Enplegu publikoan behin-behinekotasuna murrizteko premiazko neurriei buruzko uztailaren 6ko 14/2021 Errege Lege Dekretuak, 2. artikuluan, aldi baterako enplegua egonkortzeko prozesu berriak aurreikusten ditu, administrazio publikoetan dagoen gehiegizko behin-behinekotasunari aurre egiteko eta Europar Batasunak gure herrialdeari ildo horretan emandako jarraibideak betetzeko. Artikulu honetan, aldi baterako enplegua egonkortzeko prozesu horiei aplikatu beharreko araubide juridikoa aztertzen da, eta, bereziki, aldi baterako enplegua egonkortzeko prozesuetan sartuta dauden bitarteko funtzionarioen edo aldi baterako lan-kontratuko langileen alde aitortzen den konpentsazio ekonomikoa, baldin eta, halakotzat jardunean egonik eta egonkortzeko hautaketa-prozesuan parte hartu ondoren, Administrazioarekin zuen harremana amaituta ikusten badu hautaketa-prozesua ez gainditzeagatik, hautapen-probak aukerakoak edo nahitaezkoak izateagatik, aldi baterako enplegua egonkortzeko prozesuengatik, balorazio-notengatik eta balorazio-sistemengatik. Art. 2 of Royal Decree-Law 14/2021, of July 6, on urgent measures to reduce the use of temporary contracts in public employment, provides for new stabilization processes for temporary employment to tackle the excessive use of temporary contracts at public administration bodies and comply with the indications of the European Union in Spain in this regard. This article studies the legal regime applicable to these temporary employment stabilization processes, and in particular, the economic compensation provided for temporary civil servants or temporary employees affected by temporary employment stabilization processes who, while in active employment as such and having participated in the selective stabilization process, find their relationship with the administration terminated due to their failure to pass the selection process, the optional or mandatory nature of the temporary employment stabilization processes, the selective systems, the assessment of merits, tests and the cut-off grades.

Edge current and pairing order transition in chiral bacterial vortices

Bacterial suspensions show turbulence-like spatiotemporal dynamics and vortices moving irregularly inside the suspensions. Understanding these ordered vortices is an ongoing challenge in active matter physics, and their application to the control of autonomous material transport will provide significant development in microfluidics. Despite the extensive studies, one of the key aspects of bacterial propulsion has remained elusive: The motion of bacteria is chiral, i.e., it breaks mirror symmetry. Therefore, the mechanism of control of macroscopic active turbulence by microscopic chirality is still poorly understood. Here, we report the selective stabilization of chiral rotational direction of bacterial vortices in achiral circular microwells sealed by an oil/water interface. The intrinsic chirality of bacterial swimming near the top and bottom interfaces generates chiral collective motions of bacteria at the lateral boundary of the microwell that are opposite in directions. These edge currents grow stronger as bacterial density increases, and, within different top and bottom interfaces, their competition leads to a global rotation of the bacterial suspension in a favored direction, breaking the mirror symmetry of the system. We further demonstrate that chiral edge current favors corotational configurations of interacting vortices, enhancing their ordering. The intrinsic chirality of bacteria is a key feature of the pairing order transition from active turbulence, and the geometric rule of pairing order transition may shed light on the strategy for designing chiral active matter.

A Calcium/Palmitoylation Switch Interfaces the Signaling Networks of Stress Response and Transition to Flowering

The precise timing of flowering in adverse environments is critical for plants to secure reproductive success. We report a novel mechanism controlling the time of flowering by which the palmitoylation-dependent nuclear import of protein SOS3/CBL4, a Ca2+-signaling intermediary in the plant response to salinity, results in the selective stabilization of the flowering time regulator GIGANTEA inside the nucleus under salt stress, while degradation of GIGANTEA in the cytosol releases the protein kinase SOS2 to achieve salt tolerance. Salinity stress enhanced the palmytoilation and nuclear localization of SOS3/CBL4, which then interacted with the photoperiodic flowering components GIGANTEA and FKF1 on the CONSTANS gene promoter to sustain expression. Thus, SOS3 acts as a Ca2+- and palmitoylation-dependent molecular switch that fine-tunes flowering in a saline environment through the shared spatial separation and selective stabilization of GIGANTEA. The SOS3 protein connects two signaling networks to co-regulate stress adaptation and time of flowering.

Resolving the Ultrafast Dynamics of the Anionic Green Fluorescent Protein Chromophore in Water

The chromophore of the green fluorescent protein (GFP) is critical for probing environmental influences on fluorescent protein behavior. Using the aqueous system as a bridge between the unconfined vacuum system and a constricting protein scaffold, we investigate the steric and electronic effects of the environment on the photodynamical behavior of the chromophore. Specifically, we perform <i>ab initio </i>multiple spawning to simulate five picoseconds of nonadiabatic dynamics after photoexcitation, resolving the excited-state pathways responsible for internal conversion in the aqueous chromophore. We identify an ultrafast pathway that proceeds through a short-lived (sub-picosecond) imidazolinone-twisted (I-twisted) species and a slower (several picoseconds) channel that proceeds through a long-lived phenolate-twisted (P-twisted) intermediate. The molecule navigates the non-equilibrium energy landscape via an aborted hula-twist-like motion towards the one-bond-flip dominated conical intersection seams, as opposed to following the pure one-bond-flip paths proposed by the excited-state equilibrium picture. We interpret our simulations in the context of time-resolved fluorescence experiments, which use short and long time components to describe the fluorescence decay of the aqueous GFP chromophore. Our results suggest that the longer time component is caused by an energetically uphill approach to the P-twisted intersection seam rather than an excited-state barrier to reach the twisted intramolecular charge transfer species. Irrespective of the location of the non-adiabatic population events, the twisted intersection seams are inefficient at facilitating isomerization in aqueous solution. The disordered and homogeneous nature of the aqueous solvent environment facilitates non-selective stabilization with respect to I- and P-twisted species, offering an important foundation for understanding the consequences of selective stabilization in heterogeneous and rigid protein environments.

Resolving the Ultrafast Dynamics of the Anionic Green Fluorescent Protein Chromophore in Water

The chromophore of the green fluorescent protein (GFP) is critical for probing environmental influences on fluorescent protein behavior. Using the aqueous system as a bridge between the unconfined vacuum system and a constricting protein scaffold, we investigate the steric and electronic effects of the environment on the photodynamical behavior of the chromophore. Specifically, we perform <i>ab initio </i>multiple spawning to simulate five picoseconds of nonadiabatic dynamics after photoexcitation, resolving the excited-state pathways responsible for internal conversion in the aqueous chromophore. We identify an ultrafast pathway that proceeds through a short-lived (sub-picosecond) imidazolinone-twisted (I-twisted) species and a slower (several picoseconds) channel that proceeds through a long-lived phenolate-twisted (P-twisted) intermediate. The molecule navigates the non-equilibrium energy landscape via an aborted hula-twist-like motion towards the one-bond-flip dominated conical intersection seams, as opposed to following the pure one-bond-flip paths proposed by the excited-state equilibrium picture. We interpret our simulations in the context of time-resolved fluorescence experiments, which use short and long time components to describe the fluorescence decay of the aqueous GFP chromophore. Our results suggest that the longer time component is caused by an energetically uphill approach to the P-twisted intersection seam rather than an excited-state barrier to reach the twisted intramolecular charge transfer species. Irrespective of the location of the non-adiabatic population events, the twisted intersection seams are inefficient at facilitating isomerization in aqueous solution. The disordered and homogeneous nature of the aqueous solvent environment facilitates non-selective stabilization with respect to I- and P-twisted species, offering an important foundation for understanding the consequences of selective stabilization in heterogeneous and rigid protein environments.