The Exosome Subunit Rrp44 Plays a Direct Role in RNA Substrate Recognition

The exosome plays key roles in RNA maturation and surveillance, but it is unclear how target RNAs are identified. We report the functional characterization of the yeast exosome component Rrp44, a member of the RNase II family. Recombinant Rrp44 and the purified TRAMP polyadenylation complex each specifically recognized tRNAiMet lacking a single m1A58 modification, even in the presence of a large excess of total tRNA. This tRNA is otherwise mature and functional in translation in vivo but is presumably subtly misfolded. Complete degradation of the hypomodified tRNA required both Rrp44 and the poly(A) polymerase activity of TRAMP. The intact exosome lacking only the catalytic activity of Rrp44 failed to degrade tRNAiMet, showing this to be a specific Rrp44 substrate. Recognition of hypomodified tRNAiMet by Rrp44 is genetically separable from its catalytic activity on other substrates, with the mutations mapping to distinct regions of the protein

A heterozygous variant in the human cardiac miR-133 gene, MIR133A2, alters miRNA duplex processing and strand abundance

BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Sequential cleavage of miRNA precursors results in a ~22 nucleotide duplex of which one strand, the mature miRNA, is typically loaded into the RNA-induced silencing complex (RISC) while the passenger strand is degraded. Very little is known about how genetic variation might affect miRNA biogenesis and function. RESULTS We re-sequenced the MIR1-1, MIR1-2, MIR133A1, MIR133A2, and MIR133B genes, that encode the cardiac-enriched miRNAs, miR-1 and miR-133, in 120 individuals with familial atrial fibrillation and identified 10 variants, including a novel 79T > C MIR133A2 substitution. This variant lies within the duplex at the 3' end of the mature strand, miR-133a-3p, and is predicted to prevent base-pairing and weaken thermostability at this site, favoring incorporation of the passenger strand, miR-133a-5p, into RISC. Genomic DNA fragments containing miR-133a-2 precursor sequences with 79T and 79C alleles were transfected into HeLa cells. On Northern blotting the 79T allele showed strong expression of miR-133a-3p with weak expression of miR-133a-5p. In contrast, the 79C allele had no effect on miR-133a-3p but there was a significant increase (mean 3.6-fold) in miR-133a-5p levels. Deep sequencing of small RNA libraries prepared from normal human and murine atria confirmed that nearly all the mature miR-133a was comprised of miR-133a-3p and that levels of miR-133a-5p were very low. A number of isomiRs with variations at 5' and 3' ends were identified for both miR-133a-3p and miR-133a-5p, with 2 predominant miR-133a-3p isomiRs and one predominant miR-133a-5p isomiR. Bioinformatics analyses indicate that the major miR-133a-3p and 5p isomiRs have numerous predicted target mRNAs, only a few of which are in common. CONCLUSIONS Multiple miR-133a isomiRs with potential different mRNA target profiles are present in the atrium in humans and mice. We identified a human 79T > C MIR133A2 variant that alters miRNA processing and results in accumulation of the miR-133a-5p strand that is usually degraded

Solution of an infection model near threshold

We study the Susceptible-Infected-Recovered model of epidemics in the vicinity of the threshold infectivity. We derive the distribution of total outbreak size in the limit of large population size $N$. This is accomplished by mapping the problem to the first passage time of a random walker subject to a drift that increases linearly with time. We recover the scaling results of Ben-Naim and Krapivsky that the effective maximal size of the outbreak scales as $N^{2/3}$, with the average scaling as $N^{1/3}$, with an explicit form for the scaling function

Recent advances in modelling the ocean circulation and its effects on climate

The authors aim to acquaint the reader with the current state of ocean circulation models, their ability to model the present climate state and its variability, and their major shortcomings and uncertainties. They limit the discussion to three-dimensional models of the physical system. They begin by describing the basic structure of circulation models, and discussing various problems with their implementation. They give a brief overview of the types of observational data in oceanography, and the ways in which the data are used. Some results from models of the wind-driven circulation are discussed, with particular emphasis on the dynamics of mesoscale eddies. Considerable progress has been made in understanding short-term variability associated with ENSO, and the authors describe ocean-atmosphere interactions in the tropics as well as results from coupled ocean-atmosphere models for ENSO variability. Models of the thermohaline circulation are described and some emerging ideas regarding long-term changes are given

An analysis for high speed propeller-nacelle aerodynamic performance prediction. Volume 1: Theory and application

A computer program, the Propeller Nacelle Aerodynamic Performance Prediction Analysis (PANPER), was developed for the prediction and analysis of the performance and airflow of propeller-nacelle configurations operating over a forward speed range inclusive of high speed flight typical of recent propfan designs. A propeller lifting line, wake program was combined with a compressible, viscous center body interaction program, originally developed for diffusers, to compute the propeller-nacelle flow field, blade loading distribution, propeller performance, and the nacelle forebody pressure and viscous drag distributions. The computer analysis is applicable to single and coaxial counterrotating propellers. The blade geometries can include spanwise variations in sweep, droop, taper, thickness, and airfoil section type. In the coaxial mode of operation the analysis can treat both equal and unequal blade number and rotational speeds on the propeller disks. The nacelle portion of the analysis can treat both free air and tunnel wall configurations including wall bleed. The analysis was applied to many different sets of flight conditions using selected aerodynamic modeling options. The influence of different propeller nacelle-tunnel wall configurations was studied. Comparisons with available test data for both single and coaxial propeller configurations are presented along with a discussion of the results

An analysis for high speed propeller-nacelle aerodynamic performance prediction. Volume 2: User's manual

A user's manual for the computer program developed for the prediction of propeller-nacelle aerodynamic performance reported in, An Analysis for High Speed Propeller-Nacelle Aerodynamic Performance Prediction: Volume 1 -- Theory and Application, is presented. The manual describes the computer program mode of operation requirements, input structure, input data requirements and the program output. In addition, it provides the user with documentation of the internal program structure and the software used in the computer program as it relates to the theory presented in Volume 1. Sample input data setups are provided along with selected printout of the program output for one of the sample setups

SLC36 family of proton-coupled amino acid transporters in GtoPdb v.2023.1

Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives [29, 30]. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma-membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [4]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2, 26]. PAT2 is expressed at the apical membrane of the renal proximal tubule [7] and at the plasma-membrane in brown/beige adipocytes [31]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [12, 28]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references [3]

SLC36 family of proton-coupled amino acid transporters in GtoPdb v.2021.3

Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma-membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [3]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2, 18]. PAT2 is expressed at the apical membrane of the renal proximal tubule [6] and at the plasma-membrane in brown/beige adipocytes [20]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [11]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references [3]

SLC36 family of proton-coupled amino acid transporters (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Members of the SLC36 family of proton-coupled amino acid transporters are involved in membrane transport of amino acids and derivatives. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma-membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [3]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [2, 15]. PAT2 is expressed at the apical membrane of the renal proximal tubule [5] and at the plasma-membrane in brown/beige adipocytes [17]. PAT1 and PAT4 are involved in regulation of the mTORC1 pathway [8]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references