Highlighting the importance of biodiversity conservation through the Holy Qur'an.

Religious environmentalism relies upon religious texts and leadership to promote effective and long-lasting change for environmental problems, such as responsible use and conservation of natural resources and biodiversity. World religions note the importance of biodiversity and humanity's responsibility in stewarding biodiversity as a member of ecological communities. We reviewed Quranic verses that relate to biodiversity and align with United Nations Sustainable Development Goals (SDGs). The Holy Quran was reviewed in electronic and hard copy formats, and verses related to biodiversity were translated to English and tabulated by Qur'anic chapter, verse, and narrative citation. Twenty-one Qur'anic verses were identified that addressed biodiversity. Scriptures were divided into 5 groups that addressed provision of resources, governance or stewardship of resources, nature as a teacher, and human life in nature's communities or described creation of biodiversity. Qur'anic verses were aligned with 4 SDGs (goals 12-15), which address sustainable consumption of natural resources, global climate change, life in marine environments, and life in terrestrial environments, including freshwater ecosystems. This alignment demonstrates the interconnectedness of life, that conservation of biodiversity is referenced in the Quran, and how positive management of natural recourses can be beneficial to Muslim communities on local, national, and global scales. Positive movement toward ecofriendly practices, sound environmental resource use and management, biodiversity conservation, and governmental policies on conservation can be promoted through scriptures from the Holy Qur'an.

Énfasis en la importancia de la conservación de la biodiversidad con el Sagrado Corán Resumen El ambientalismo religioso depende de los textos y el liderazgo religioso para promover un cambio efectivo y duradero de los problemas ambientales, como el uso y conservación de los recursos naturales y la biodiversidad. Las religiones del mundo destacan la importancia de la biodiversidad y la responsabilidad de la humanidad en el cuidado de la biodiversidad como miembros de las comunidades ecológicas. Revisamos los versos del Corán que se relacionan con la biodiversidad y que se alinean con los Objetivos de Desarrollo Sustentable (ODGs) de las Naciones Unidas. Revisamos el Sagrado Corán en formato físico y electrónico y tradujimos al inglés los versos relacionados con la biodiversidad para luego tabularlos según la cita del capítulo, verso y narrativa del Corán. Identificamos 21 versos del Corán en los que se aborda la biodiversidad. Clasificamos las escrituras en cinco grupos de acuerdo con si abordan el suministro de recursos, la administración o cuidado de los recursos, a la naturaleza como docente y a la vida humana dentro de las comunidades naturales o si describen la creación de la biodiversidad. Los versos del Corán se alinearon con cuatro de los ODGs (del 12 al 15), lo cuales abordan el consumo sustentable de los recursos naturales, el cambio climático mundial y la vida marina y terrestre, incluyendo los ecosistemas de agua dulce. Esta alineación demuestra la interconexión de la vida, que el Corán tiene referencias a la conservación de la biodiversidad y cómo la gestión positiva de los recursos naturales puede ser benéfica para las comunidades musulmanes a escala local, nacional y mundial. El Sagrado Corán puede usarse para promover un movimiento positivo hacia las prácticas amigables con el ambiente, el uso y manejo sensato de los recursos naturales, la conservación de la biodiversidad y políticas gubernamentales para la conservación.

Human oncoprotein 5MP suppresses general and repeat-associated non-AUG translation via eIF3 by a common mechanism.

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. In Drosophila, 5MP/Kra represses neuronal toxicity and enhances the lifespan in an FXTAS disease model. These results implicate 5MP in protecting cells from unwanted byproducts of non-AUG translation in neurodegeneration.

Novel oncogene 5MP1 reprograms c-Myc translation initiation to drive malignant phenotypes in colorectal cancer.

BACKGROUND: Translational reprogramming through controlled initiation from non-AUG start codons is considered a crucial driving force in tumorigenesis and tumor progression. However, its clinical impact and underlying mechanism are not fully understood. METHODS: Using a bioinformatics approach, we identified translation initiation regulator 5MP1/BZW2 on chromosome 7p as a potential oncogenic driver gene in colorectal cancer (CRC), and explored the biological effect of 5MP1 in CRC in vitro or in vivo. Pathway analysis was performed to identify the downstream target of 5MP1, which was verified with transcriptomic and biochemical analyses. Finally, we assessed the clinical significance of 5MP1 expression in CRC patients. FINDINGS: 5MP1 was ubiquitously amplified and overexpressed in CRC. 5MP1 promoted tumor growth and induced cell cycle progression of CRC. c-Myc was identified as its potential downstream effector. c-Myc has two in-frame start codons, AUG and CUG (non-AUG) located upstream of the AUG. 5MP1 expression increased the AUG-initiated c-Myc isoform relative to the CUG-initiated isoform. The AUG-initiated c-Myc isoform displayed higher protein stability and a stronger transactivation activity for oncogenic pathways than the CUG-initiated isoform, accounting for 5MP1-driven cell cycle progression and tumor growth. Clinically, high 5MP1 expression predicts poor survival of CRC patients. INTERPRETATION: 5MP1 is a novel oncogene that reprograms c-Myc translation in CRC. 5MP1 could be a potential therapeutic target to overcome therapeutic resistance conferred by tumor heterogeneity of CRC. FUND: Japan Society for the Promotion of Science; Priority Issue on Post-K computer; National Institutes of Health; National Science Foundation; KSU Johnson Cancer Center.

Competition between translation initiation factor eIF5 and its mimic protein 5MP determines non-AUG initiation rate genome-wide.

In the human genome, translation initiation from non-AUG codons plays an important role in various gene regulation programs. However, mechanisms regulating the non-AUG initiation rate remain poorly understood. Here, we show that the non-AUG initiation rate is nearly consistent under a fixed nucleotide context in various human and insect cells. Yet, it ranges from <1% to nearly 100% compared to AUG translation, depending on surrounding sequences, including Kozak, and possibly additional nucleotide contexts. Mechanistically, this range of non-AUG initiation is controlled in part, by the eIF5-mimic protein (5MP). 5MP represses non-AUG translation by competing with eIF5 for the Met-tRNAi-binding factor eIF2. Consistently, eIF5 increases, whereas 5MP decreases translation of NAT1/EIF4G2/DAP5, whose sole start codon is GUG. By modulating eIF5 and 5MP1 expression in combination with ribosome profiling we identified a handful of previously unknown non-AUG initiation sites, some of which serve as the exclusive start codons. If the initiation rate for these codons is low, then an AUG-initiated downstream ORF prevents the generation of shorter, AUG-initiated isoforms. We propose that the homeostasis of the non-AUG translatome is maintained through balanced expression of eIF5 and 5MP.

Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions.