Stimulated cells and cancer cells have widespread shortening of mRNA 3'-untranslated regions (3'UTRs) and switches to shorter mRNA isoforms due to usage of more proximal polyadenylation signals (PASs) in introns and last exons. U1 snRNP (U1), vertebrates' most abundant non-coding (spliceosomal) small nuclear RNA, silences proximal PASs and its inhibition with antisense morpholino oligonucleotides (U1 AMO) triggers widespread premature transcription termination and mRNA shortening. Here we show that low U1 AMO doses increase cancer cells' migration and invasion in vitro by up to 500%, whereas U1 overexpression has the opposite effect. In addition to 3'UTR length, numerous transcriptome changes that could contribute to this phenotype are observed, including alternative splicing, and mRNA expression levels of proto-oncogenes and tumor suppressors. These findings reveal an unexpected role for U1 homeostasis (available U1 relative to transcription) in oncogenic and activated cell states, and suggest U1 as a potential target for their modulation.

Contact angle hysteresis is an important physical phenomenon. It is omnipresent in nature and also plays a crucial role in various industrial processes. Despite its relevance, there is a lack of consensus on how to incorporate a description of contact angle hysteresis into physical models. To clarify this, starting from the basic definition of contact angle hysteresis, we introduce the formalism and models for implementing contact angle hysteresis into relevant physical phenomena. Furthermore, we explain the role of the contact angle hysteresis on physical phenomena relevant for industrial applications such as sliding drops, coffee stains phenomenon (in general evaporative self-assembly), curtain and wire coating techniques.

Liquid drops hitting solid surfaces deform substantially under the influence of the ambient air that needs to be squeezed out before the liquid actually touches the solid. Nanometer-and microsecond-resolved dual wavelength interferometry reveals a complex evolution of the interface between the drop and the gas layer underneath. For intermediate impact speeds (We $ 1 . . . 10) the layer thickness can develop one or two local minima-reproduced in numerical calculations-that eventually lead to the nucleation of solidliquid contact at a We-dependent radial position, from a film thickness >200 nm. Solid-liquid contact spreads at a speed involving capillarity, liquid viscosity and inertia. DOI: 10.1103/PhysRevLett.108.074505 PACS numbers: 47.55.DÀ, 47.55.nd, 47.55.np Liquid drops deform substantially upon impact onto a solid surface. Depending on impact speed they rebound, get deposited on the surface, or disintegrate in a splash (for a review, see Ref.[1]). Following experimental reports of tiny air bubbles being incorporated into drops [2][3][4][5] as well as the suppression of splashing upon reducing the ambient air pressure [6] it became clear that the ambient air plays a non-negligible role in the impact process. To describe the expulsion of the air that initially separates the drop from the solid, several models were formulated [7-9] that describe the drop impact primarily in terms of a balance between the inertia of the decelerating liquid and the excess pressure arising from the viscous squeezeout of the thin air layer. A local pressure maximum right under the drop leads to the formation of a ''dimple'', which should eventually evolve into the enclosed air bubble [9]. Using this model and including corrections due to capillary forces, it was shown that a thin air film of almost constant thickness should develop under the drop [10], and the formation of a thin liquid jet was observed using an axisymmetric, curvilinear description [11]. Mandre et al. [10] suggested that this air film plays an important role, e.g., for the splashing process, but recent experiments by Discroll and Nagel [12] question this scenario: while the presence of interference fringes right under the drop indeed confirms the formation of a dimple, their measurements suggest that direct liquid-solid contact forms very quickly around the dimple, separating dimple from splashing dynamics. Whether air films do play an important role in other regimes of drop impact, how they collapse to establish direct liquid-solid contact, and to what extent the proposed visco-inertial models describe these processes remains unexplored at this stage.In this letter, we address these issues by monitoring the evolution and the collapse of the air film for a wide range of liquid properties (interfacial tension , viscosity l , density l ) at moderate impact speeds. To do so, we develop an advanced high-speed dual wavelength interferometry technique that allows us to extract full thickness profiles with an unprecedented resolution of % 10 nm and 50 s. Focusing on...

U1 snRNP (U1) functions in splicing introns and telescripting, which suppresses premature cleavage and polyadenylation (PCPA). Using U1 inhibition in human cells, we show that U1 telescripting is selectively required for sustaining long-distance transcription elongation in introns of large genes (median 39 kb). Evidence of widespread PCPA in the same locations in normal tissues reveals that large genes incur natural transcription attrition. Underscoring the importance of U1 telescripting as a gene-size-based mRNA-regulation mechanism, small genes were not sensitive to PCPA, and the spliced-mRNA productivity of ~1,000 small genes (median 6.8 kb) increased upon U1 inhibition. Notably, these small, upregulated genes were enriched in functions related to acute stimuli and cell-survival response, whereas genes subject to PCPA were enriched in cell-cycle progression and developmental functions. This gene size–function polarization increased in metazoan evolution by enormous intron expansion. We propose that telescripting adds an overarching layer of regulation to size–function-stratified genomes, leveraged by selective intron expansion to rapidly shift gene expression priorities.