Newly made messenger RNAs are processed and packaged into ribonucleoprotein complexes (mRNPs) and recognized by the essential transcription-export complex (TREX) for nuclear export 1,2 . However, the mechanisms of mRNP recognition and three-dimensional organization are poorly understood 3 . Here, we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the two-megadalton TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon-junction complexes. Exon-junction complexes can multimerize through ALYREF, suggesting a mechanism for mRNP organization. Endogenous mRNPs form compact 'globules' that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact, and protect mRNAs to promote their packaging for nuclear export. The mRNP globule organization provides a framework to understand how mRNP architecture could facilitate mRNA biogenesis and export. This work is licensed under a CC BY 4.0 International license.
The Caribbean soft coral Erythropodium caribaeorum is a rich source of erythrolides—chlorinated briarane diterpenoids. These compounds have an ecological role as feeding deterrents, with a wide variation in their composition depending on the location where the sample is collected. In Colombia, this soft coral can be found at different locations in the Caribbean Sea including Santa Marta, Islas del Rosario, and Providencia—three environmentally different coral reef areas in the south and southwest Caribbean Sea. In order to evaluate differences in erythrolide composition, the metabolic profiles of samples from each of these locations were analyzed by HPLC-MS. Principal component analysis showed changes in the diterpene composition according to the sample origin. Diterpenes from samples collected at each location were isolated to describe the three chemotypes. The chemotype from Santa Marta was highly diverse, with the new erythrolides W and X together with eight known erythrolides. The sample from Islas del Rosario showed a low diversity chemotype constituted by high amounts of erythrolide A and B. The chemotype from Providencia showed low chemical diversity with only two main compounds—erythrolide V and R. Evaluation of cytotoxic activity against the human cancer cell lines PC-3, MCF7, and A549 showed erythrolides A and B as the more active compounds with IC50 values in the range from 2.45 to 30 μM.
In tropical countries, the control of the mosquito Aedes aegypti is a public health priority due to its role as a vector of important viral diseases. Marine cyanobacteria are recognized as abundant sources of bioactive compounds, and they constitute a potential source of insecticides useful for controlling mosquito populations and preventing epidemic outbreaks. We collected 30 benthic cyanobacterial mats in Providencia and Rosario islands (in the Colombian Caribbean) belonging to the genera Phormidium, Symploca, Oscillatoria, Lyngbya, Pseudoanabaena, Leptolyngbya, Moorea, and Dapis. Fractions of organic extracts from the most abundant environmental samples were evaluated in three bioassays, assessing (i) larvicidal activity against A. aegypti, (ii) toxicity against the brine shrimp (Artemia salina) nauplii, and (iii) acetylcholinesterase inhibition. Non-polar fractions exhibited larvicidal activity. The polar fraction from one Dapis pleuosa extract showed larvicidal activity without being toxic against A. salina nauplii. Extracts from Moorea producens exhibited the greatest toxicity against A. aegypti larvae and A. salina nauplii. From 23 cultured cyanobacterial samples, only five grew under laboratory conditions and produced enough biomass to yield organic extracts. Of these, three extracts showed strong larvicidal activity, but only the extract from Phormidium tenue showed reduced toxicity against A. salina nauplii. We detected variation among the chemical profiles and larvicidal activity of cyanobacterial consortia depending on sites and dates of collection. Our findings suggest that despite variation in chemical profiles, extracts of marine benthic cyanobacteria can be further developed as effective control agents against insect vectors, in their larval stages. The culture of marine benthic cyanobacteria needs to be further explored to provide enough biomass leading to the identification of bioactive compounds with public health applications.
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