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1.
Nature ; 616(7958): 828-835, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37020021

RESUMO

Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export1,2. However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood3. Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa 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, which suggests 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 organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.


Assuntos
Transporte Ativo do Núcleo Celular , Núcleo Celular , RNA Mensageiro , Transcrição Gênica , Humanos , Núcleo Celular/genética , Núcleo Celular/metabolismo , Microscopia Crioeletrônica , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Éxons
2.
Mar Drugs ; 18(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861453

RESUMO

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.


Assuntos
Antozoários/química , Metaboloma , Animais , Antozoários/metabolismo , Região do Caribe , Colômbia , Recifes de Corais , Diterpenos/química , Humanos
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