N 6-methyladenosine (m6A) and N6, 2′-O-Dimethyladenosine (m6Am) modifications (m6A/m) of messenger RNA mediate diverse cellular functions. Oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV) has latent and lytic replication phases that are essential for the development of KSHV-associated cancers. To date, the role of m6A/m in KSHV replication and tumorigenesis is unclear. Here, we provide mechanistic insights by examining the viral and cellular m6A/m epitranscriptomes during KSHV latent and lytic infection. KSHV transcripts contain abundant m6A/m modifications during latent and lytic replication, and these modifications are highly conserved among different cell types and infection systems. Knockdown of YTHDF2 enhanced lytic replication by impeding KSHV RNA degradation. YTHDF2 binds to viral transcripts and differentially mediates their stability. KSHV latent infection induces 5′UTR hypomethylation and 3′UTR hypermethylation of the cellular epitranscriptome, regulating oncogenic and epithelial-mesenchymal transition pathways. KSHV lytic replication induces dynamic reprograming of epitranscriptome, regulating pathways that control lytic replication. These results reveal a critical role of m6A/m modifications in KSHV lifecycle and provide rich resources for future investigations.
Lateralization of function is a well-known phenomenon in humans. The two hemispheres of the human brain are functionally specialized such that certain cognitive skills, such as language or musical ability, conspecific recognition, and even emotional responses, are mediated by one hemisphere more than the other [1, 2]. Studies over the past 30 years suggest that lateralization occurs in other vertebrate species as well [3-11]. In general, lateralization is observed in different sensory modalities in humans as well as vertebrates, and there are interesting parallels (reviewed in [12]). However, little is known about functional asymmetry in invertebrates [13, 14] and there is only one investigation in insects [15]. Here we show, for the first time, that the honeybee Apis mellifera displays a clear laterality in responding to learned odors. By training honeybees on two different versions of the well-known proboscis extension reflex (PER) paradigm [16, 17], we demonstrate that bees respond to odors better when they are trained through their right antenna. To our knowledge, this is the first demonstration of asymmetrical learning performance in an insect.
Although the numerical abilities of many vertebrate species have been investigated in the scientific literature, there are few convincing accounts of invertebrate numerical competence. Honeybees, Apis mellifera, by virtue of their other impressive cognitive feats, are a prime candidate for investigations of this nature. We therefore used the well-established delayed match-to-sample paradigm, to test the limits of honeybees' ability to match two visual patterns solely on the basis of the shared number of elements in the two patterns. Using a y-maze, we found that bees can not only differentiate between patterns containing two and three elements, but can also use this prior knowledge to differentiate three from four, without any additional training. However, bees trained on the two versus three task could not distinguish between higher numbers, such as four versus five, four versus six, or five versus six. Control experiments confirmed that the bees were not using cues such as the colour of the exact configuration of the visual elements, the combined area or edge length of the elements, or illusory contours formed by the elements. To our knowledge, this is the first report of number-based visual generalisation by an invertebrate.
In principle, there are two strategies for navigating a straight course. One is to use an external directional reference and continually reorienting with reference to it, while the other is to infer body rotations from internal sensory information only. We show here that, while the first strategy will enable an animal or mobile agent to move arbitrarily far away from its starting point, the second strategy will not do so, even after an infinite number of steps. Thus, an external directional reference-some form of compass-is indispensable for ensuring progress away from home. This limitation must place significant constraints on the evolution of biological navigation systems. Some specific examples are discussed. An important corollary arising from the analysis of compassless navigation is that the maximum expected displacement represents a robust measure of the straightness of a path.
Methyltranscriptome is an exciting new area that studies the mechanisms and functions of methylation in transcripts. A knowledge base with the systematic collection and curation of context specific transcriptome-wide methylations is critical for elucidating their biological functions as well as for developing bioinformatics tools. Since its inception in 2014, the Met-DB (Liu, H., Flores, M.A., Meng, J., Zhang, L., Zhao, X., Rao, M.K., Chen, Y. and Huang, Y. (2015) MeT-DB: a database of transcriptome methylation in mammalian cells. Nucleic Acids Res., 43, D197–D203), has become an important resource for methyltranscriptome, especially in the N6-methyl-adenosine (m6A) research community. Here, we report Met-DB v2.0, the significantly improved second version of Met-DB, which is entirely redesigned to focus more on elucidating context-specific m6A functions. Met-DB v2.0 has a major increase in context-specific m6A peaks and single-base sites predicted from 185 samples for 7 species from 26 independent studies. Moreover, it is also integrated with a new database for targets of m6A readers, erasers and writers and expanded with more collections of functional data. The redesigned Met-DB v2.0 web interface and genome browser provide more friendly, powerful, and informative ways to query and visualize the data. More importantly, MeT-DB v2.0 offers for the first time a series of tools specifically designed for understanding m6A functions. Met-DB V2.0 will be a valuable resource for m6A methyltranscriptome research. The Met-DB V2.0 database is available at http://compgenomics.utsa.edu/MeTDB/ and http://www.xjtlu.edu.cn/metdb2.
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