The association of Alu repeats with the generation of potential AU-rich elements (ARE) at 3' untranslated regions.

BACKGROUND: A significant portion (about 8% in the human genome) of mammalian mRNA sequences contains AU (Adenine and Uracil) rich elements or AREs at their 3' untranslated regions (UTR). These mRNA sequences are usually stable. However, an increasing number of observations have been made of unstable species, possibly depending on certain elements such as Alu repeats. ARE motifs are repeats of the tetramer AUUU and a monomer A at the end of the repeats ((AUUU)(n)A). The importance of AREs in biology is that they make certain mRNA unstable. Proto-oncogene, such as c-fos, c-myc, and c-jun in humans, are associated with AREs. Although it has been known that the increased number of ARE motifs caused the decrease of the half-life of mRNA containing ARE repeats, the exact mechanism is as of yet unknown. We analyzed the occurrences of AREs and Alu and propose a possible mechanism for how human mRNA could acquire and keep AREs at its 3' UTR originating from Alu repeats. RESULTS: Interspersed in the human genome, Alu repeats occupy 5% of the 3' UTR of mRNA sequences. Alu has poly-adenine (poly-A) regions at its end, which lead to poly-thymine (poly-T) regions at the end of its complementary Alu. It has been found that AREs are present at the poly-T regions. From the 3' UTR of the NCBI's reference mRNA sequence database, we found nearly 40% (38.5%) of ARE (Class I) were associated with Alu sequences (Table 1) within one mismatch allowance in ARE sequences. Other ARE classes had statistically significant associations as well. This is far from a random occurrence given their limited quantity. At each ARE class, random distribution was simulated 1,000 times, and it was shown that there is a special relationship between ARE patterns and the Alu repeats. CONCLUSION: AREs are mediating sequence elements affecting the stabilization or degradation of mRNA at the 3' untranslated regions. However, AREs' mechanism and origins are unknown. We report that Alu is a source of ARE. We found that half of the longest AREs were derived from the poly-T regions of the complementary Alu

EP240801a/XRF 240801B: An X-ray Flash Detected by the Einstein Probe and Implications of its Multiband Afterglow

We present multiband observations and analysis of EP240801a, a low-energy, extremely soft gamma-ray burst (GRB) discovered on August 1, 2024 by the Einstein Probe (EP) satellite, with a weak contemporaneous signal also detected by Fermi/GBM. Optical spectroscopy of the afterglow, obtained by GTC and Keck, identified the redshift of $z = 1.6734$. EP240801a exhibits a burst duration of 148 s in X-rays and 22.3 s in gamma-rays, with X-rays leading by 80.61 s. Spectral lag analysis indicates the gamma-ray signal arrived 8.3 s earlier than the X-rays. Joint spectral fitting of EP/WXT and Fermi/GBM data yields an isotropic energy $E_{\gamma,\rm{iso}} = (5.57^{+0.54}_{-0.50})\times 10^{51}\,\rm{erg}$, a peak energy $E_{\rm{peak}} =14.90^{+7.08}_{-4.71}\,\rm{keV}$, a fluence ratio $\rm S(25-50\,\rm{keV})/S(50-100\,\rm{keV}) = 1.67^{+0.74}_{-0.46}$, classifying EP240801a as an X-ray flash (XRF). The host-galaxy continuum spectrum, inferred using Prospector, was used to correct its contribution for the observed outburst optical data. Unusual early $R$-band behavior and EP/FXT observations suggest multiple components in the afterglow. Three models are considered: two-component jet model, forward-reverse shock model and forward-shock model with energy injection. Both three provide reasonable explanations. The two-component jet model and the energy injection model imply a relatively small initial energy and velocity of the jet in the line of sight, while the forward-reverse shock model remains typical. Under the two-component jet model, EP240801a may resemble GRB 221009A (BOAT) if the bright narrow beam is viewed on-axis. Therefore, EP240801a can be interpreted as an off-beam (narrow) jet or an intrinsically weak GRB jet. Our findings provide crucial clues for uncovering the origin of XRFs

Dissection of Dom34–Hbs1 reveals independent functions in two RNA quality control pathways

International audienceEukaryotic cells have several quality control pathways that rely on translation to detect and degrade defective RNAs. Dom34 and Hbs1 are two proteins that are related to translation termination factors and are involved in no-go decay (NGD) and nonfunctional 18S ribosomal RNA (rRNA) decay (18S NRD) pathways that eliminate RNAs that cause strong ribosomal stalls. Here we present the structure of Hbs1 with and without GDP and a low-resolution model of the Dom34-Hbs1 complex. This complex mimics complexes of the elongation factor and transfer RNA or of the translation termination factors eRF1 and eRF3, supporting the idea that it binds to the ribosomal A-site. We show that nucleotide binding by Hbs1 is essential for NGD and 18S NRD. Mutations in Hbs1 that disrupted the interaction between Dom34 and Hbs1 strongly impaired NGD but had almost no effect on 18S NRD. Hence, NGD and 18S NRD could be genetically uncoupled, suggesting that mRNA and rRNA in a stalled translation complex may not always be degraded simultaneously