Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root oncogenic translational programmes. It remains unclear how these recruit and activate unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs allowing local structural rearrangement in cells. Our data demonstrate contain AG-rich within 5'UTR which structure This mode regulation is used by encoding components...

Abstract Background Regulation of the mRNA life cycle is central to gene expression control and determination cell fate. miRNAs represent a critical regulatory mechanism, but despite decades research, their mode action still not fully understood. Results Here, we show that eIF4A2 major effector repressive miRNA pathway functioning via Ccr4-Not complex. We demonstrate while DDX6 interacts with Ccr4-Not, its effects in mechanism are as pronounced. Through interaction complex, represses mRNAs...

Ubiquitination typically involves covalent linking of ubiquitin (Ub) to a lysine residue on protein substrate. Recently, new facets this process have emerged, including Ub modification non-proteinaceous substrates like ADP-ribose by the DELTEX E3 ligase family. Here, we show that family member DTX3L expands substrate repertoire include single-stranded DNA and RNA. Although N-terminal region contains nucleic acid binding domains motifs, minimal catalytically competent fragment comprises...

Ubiquitination typically involves covalent linking of ubiquitin (Ub) to a lysine residue on protein substrate. Recently, new facets this process have emerged, including Ub modification non-proteinaceous substrates like ADP-ribose by the DELTEX E3 ligase family. Here, we show that family member DTX3L expands substrate repertoire include single-stranded DNA and RNA. Although N-terminal region contains nucleic acid binding domains motifs, minimal catalytically competent fragment comprises...

Abstract RNA binding proteins drive proliferation and tumorigenesis by regulating the translation stability of specific subsets messenger RNAs (mRNAs). We have investigated role eukaryotic initiation factor 4B (eIF4B) in this process identify 10-fold more sites for eIF4B tumour cells from patients with diffuse large B-cell lymphoma compared to control B and, using individual-nucleotide resolution UV cross-linking immunoprecipitation, find that binds entire length mRNA transcripts. stimulates...

A central aspect of current virology is to define the function cellular proteins (host factors) that support viral multiplication process. This study aimed at characterizing assist RNA replication process prevalent human pathogen West Nile virus (WNV). Using in vitro and cell-based approaches, we defined p45 isoform AU-rich element RNA-binding protein 1 (AUF1) as a host factor enables efficient WNV replication. It was demonstrated AUF1 has an chaperone activity, which aids structural...

Significance Middle ear ossicles are critical for audition and rarely preserved in fossils. Based on microcomputed tomography images, our comparative 3D shape analysis of Neandertal shows striking differences between Neandertals anatomically modern humans (AMHs). However, these morphological do not affect the functional properties ossicles, potentially indicating consistent aspects vocal communication AMHs. Instead, a strong relationship ossicle morphology tympanic cavity architecture is found.

Abstract The mammalian target of rapamycin (mTOR) is a critical regulator cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities mTOR control protein synthesis machinery. This achieved, in part, via co-ordinated regulation mRNAs that contain terminal oligopyrimidine tract (TOP) at their 5′ends, although mechanisms by which this occurs are still unclear. We used RNA-binding (RBP) capture to identify changes protein-RNA interaction landscape...

Many investigations of the biosynthesis ribosomes have revealed that ribosome numbers increase with growth rate in a parallel fashion.However, we now shown there is also need for active synthesis nonmitotic tissue which induced to secrete.The paragonial glands Drosophila melanogaster produce and secrete proteins are found seminal fluid.Following even single copulation event these substantially reduced size, but rapidly refill, synthesizing new secretion (Chen, P. S. 1980) Invertebrate...

The efficiency of vibroplasty (coupler-floating mass transducer [FMT] assembly) can be monitored by direct stimulation the inner ear through active middle-ear implant system and comparison in vivo threshold postoperative bone-conduction pure-tone threshold. aim this study was to compare with speech recognition patients a high preoperative maximum word score.Retrospective cohort German-speaking implanted vibrating ossicular prosthesis (VORP) 502 or VORP 503 score between years 2011...

ABSTRACT The proliferative capacity of gland cells in Hydra attenuata was investigated. results indicate that both cell proliferation and interstitial differentiation to contribute the maintenance whole population. On basis [3H]thymidine incorporation nuclear DNA measurements, consist at least three different populations. One population consists rapidly proliferating with a cycle about 72 h. These are distributed throughout body column. In lower gastric region there is non-cycling G2 while...

ABSTRACT In previous studies, we showed that the cellular RNA-binding protein AUF1 supports replication process of flavivirus West Nile virus. Here demonstrate also enables effective proliferation dengue virus and Zika virus, indicating is a general host factor. Further studies demonstrated isoform p45 significantly stimulates initiation viral RNA protein's chaperone activity enhances interactions 5′UAR 3′UAR genome cyclization sequences. Most interestingly, observed destabilizes not only...

The CCR4-NOT complex plays an important role in the translational repression and deadenylation of mRNAs. However, little is known about specific roles interacting factors. We demonstrate that DEAD-box helicases eIF4A2 DDX6 interact directly with MA3 MIF domains CNOT1 compete for binding. Furthermore, we now show incorporation into inhibits CNOT7 activity contrast to which enhances activity. Polyadenylation tests (PAT) on endogenous mRNAs determined bound have longer poly(A) tails than...

The 3'-terminal stem-loop (3'SL) of the RNA genome flavivirus West Nile (WNV) harbors, in its stem, one sequence elements that are required for cyclization. As cyclization is a prerequisite initiation viral replication, 3'SL was proposed to act as replication silencer. lower part metastable and confers structural flexibility may regulate switch from linear circular conformation RNA. In human system, we previously demonstrated cellular RNA-binding protein, AUF1 p45, destabilizes 3'SL, exposes...

Tissue engineering strategies predominantly consist in the autologous generation of living substitutes capable restoring damaged body parts. Persisting challenges with patient-specific approaches include an inconsistent performance, high costs and delayed graft availability. Towards developing a one-for-all solution, more attractive paradigm lies exploitation dedicated cell lines for fabrication human tissue grafts. Following decellularization, this new class biomaterials relies on sole...

Abstract Phosphofructokinase (PFK) is a rate-limiting glycolytic enzyme that also possesses an unexplored RNA binding activity. Here, we show the α- and β-subunits of yeast PFK, encoded by PFK1 PFK2 , respectively, bind hundreds mRNAs in cells, including one’s coding for proteins involved regulation mitotic cell cycle. Pkf2p directly binds Mg-ATP-dependent manner to short GA-, UC-, AU- U-rich motifs overrepresented its mRNA targets. Strikingly, Pfk2p displays directional 5’ - 3’...

All mRNAs require eukaryotic translation initiation factor (eIF) 4A1 for through its different functions: loading of the pre-initiation complex onto and unwinding RNA structure. eIF4A1 is catalytic subunit cap binding eIF4F presumed to select these activities, instructed by signalling pathways driving cell fate. The mechanisms underlying activation distinct functions establish translational selectivity are unknown. Here, we have unravelled complexity mRNA selection eIF4A1. We mechanistically...

Abstract B-cell precursor acute lymphoblastic leukemias (B-ALL) are characterized by the activation of signaling pathways, which involved in survival and proliferation leukemia cells. Using an unbiased shRNA library screen enriched for targeting we identified MTOR as key gene on human B-ALL E2A-PBX1 + RCH-ACV cells dependent. genetic pharmacologic approaches, investigated whether depend upstream pathways including PI3K/AKT complexes MTORC1 or MTORC2 vitro vivo. Notably, combined inhibition...

A prerequisite for the intracellular replication process of Flavivirus West Nile virus (WNV) is cyclization viral RNA genome, which enables replicase to initiate synthesis. Our earlier studies indicated that p45 isoform cellular AU-rich element binding protein 1 (AUF1) has an chaperone activity, supports and synthesis by destabilizing a stem structure at WNV RNA's 3′-end. Here we show in mammalian cells, AUF1 consistently modified arginine methylation its C terminus. By combination different...

Oxidative stress is supposed to increase lipid accumulation by stimulation of hepatic lipogenesis at transcriptional level. This study was performed investigate the role glutathione in regulation this process. For that purpose, male rats were treated with buthionine sulfoximine (BSO), a specific inhibitor gamma-glutamylcysteine synthetase, for 7 days and compared untreated control rats.BSO treatment caused significant reduction total liver (-70%), which attributable diminished levels reduced...

The heterodimer NF90-NF45 is an RNA-binding protein complex that modulates the expression of various cellular mRNAs on post-transcriptional level. Furthermore, it acts as a host factor supports replication several RNA viruses. molecular mechanisms underlying these activities have yet to be elucidated. Recently, we showed capabilities and binding specificity NF90 considerably improves when forms with NF45. Here, demonstrate has substrate-selective chaperone activity (RCA) involving annealing...

Nuclear factor 90 (NF90) is an RNA-binding protein (RBP) that regulates post-transcriptionally the expression of various mRNAs. NF90 was recently shown to be capable discriminating between different RNA substrates. This mediated by adaptive and co-operative interplay three motifs (RBMs) in protein's C-terminus. In many cell types, exists predominantly a complex with NF45. Here, we compared properties purified monomer NF90-NF45 heterodimer biophysical biochemical means, demonstrate...

The mechanisms of how RNA binding proteins (RBP) bind to and distinguish different molecules are yet uncertain. Here, we performed a comprehensive analysis the properties multidomain RBP nuclear factor 90 (NF90) by investigating specifically functional activities two double-stranded motifs (dsRBM) an RGG motif in protein's unstructured C-terminus. By comparison affinities several NF90 variants their modes set defined molecules, turned out be very different. While dsRBM1 contributes little...