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Articles by A Jacobsen
Total Records ( 2 ) for A Jacobsen
  A Jacobsen , J Wen , D. S Marks and A. Krogh

MicroRNAs (miRNAs) and small interfering RNAs (siRNAs), bound to Argonaute proteins (RISC), destabilize mRNAs through base-pairing with the mRNA. However, the gene expression changes after perturbations of these small RNAs are only partially explained by predicted miRNA/siRNA targeting. Targeting may be modulated by other mRNA sequence elements such as binding sites for the hundreds of RNA binding proteins (RNA-BPs) expressed in any cell, and this aspect has not been systematically explored. Across a panel of published experiments, we systematically investigated to what extent sequence motifs in 3' untranslated regions (UTRs) correlate with expression changes following transfection of small RNAs. The most significantly overrepresented motifs in down-regulated mRNAs are two novel U-rich motifs (URMs), UUUUAAA and UUUGUUU, recently discovered as binding sites for the ELAVL4 (also known as HuD) RNA-BP. Surprisingly, the most significantly overrepresented motif in up-regulated mRNAs is the heptanucleotide AU-rich element (ARE), UAUUUAU, which is known to affect mRNA stability via at least 20 different RNA-BPs. We show that destabilization mediated by the transfected miRNA is generally attenuated by ARE motifs and augmented by URM motifs. These ARE and URM signatures were confirmed in different types of published experiments covering eight different cell lines. Finally, we show that both ARE and URM motifs couple to presumed endogenous miRNA binding sites in mRNAs bound by Argonaute proteins. This is the first systematic investigation of 3' UTR motifs that globally couple to regulation by miRNAs and may potentially antagonize or cooperate with miRNA/siRNA regulation. Our results suggest that binding sites of miRNAs and RNA-BPs should be considered in combination when interpreting and predicting miRNA regulation in vivo.

  K Rokkan Iversen , R Primicerio , A Larsen , J. K Egge , F Peters , O Guadayol , A Jacobsen , H Havskum and C. Marrase

Small-scale turbulence affects the pelagic food web and energy flow in marine systems and the impact is related to nutrient conditions and the assemblage of organisms present. We generated five levels of turbulence (2*10–9 to 1*10–4 W kg–1) in land-based mesocosms (volume 2.6 m3) with and without additional nutrients (31:16:1 Si:N:P µM) to asses the effect of small-scale turbulence on the lower part of the pelagic food web under different nutrient conditions. The ecological influence of nutrients and small-scale turbulence on lower trophic levels was quantified using multivariate statistics (RDA), where nutrients accounted for 31.8% of the observed biological variation, while 7.2% of the variation was explained by small-scale turbulence and its interaction with nutrients. Chlorophyll a, primary production rates, bacterial production rates and diatom and dinoflagellate abundance were positively correlated to turbulence, regardless of nutrient conditions. Abundance of autotrophic flagellates, total phytoplankton and bacteria were positively correlated to turbulence only when nutrients were added. Impact of small-scale turbulence was related to nutrient conditions, with implications for oligotrophic and eutrophic situations. The effect on community level was also different compared to single species level. Microbial processes drive biogeochemical cycles, and nutrient-controlled effects of small-scale turbulence on such processes are relevant to foresee altered carbon flow in marine systems.

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