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Science Papers on Nucleosome Retention During Transcription, LncRNA Role in Parasite Differentiation

A paper describing the structural basis of nucleosome retention during transcription elongation appears in this week's Science. Transcription requires the passage of RNA polymerase II (Pol II) through chromatin and past nucleosomes, often resulting in nucleosome displacement. How Pol II unwraps the DNA from nucleosomes to allow transcription and how DNA rewraps to retain nucleosomes, however, has been unclear. In their study, a Harvard Medical School team used cryo-electron microscopy to track the process, revealing a direct role for Pol II and transcription elongation factors in nucleosome retention and explaining how nucleosomes are retained to prevent the disruption of chromatin structure across actively transcribed genes. The work, they write, also provides a framework to understand the actions of the transcription machinery in a chromatin environment.

By sequencing the genome of Trypanosoma brucei, the parasite that causes African sleeping sickness, a group led by Universidade de Lisboa scientists has identified a long non-coding RNA (lncRNA) involved in cell differentiation in the parasite. The finding may inform future therapeutic strategies for combating T. brucei infection. In the study, which appears in Science Advances this week, the researchers used a combination of strand-specific and paired-end RNA sequencing to survey the T. brucei genome, identifying 1,428 previously uncharacterized lncRNA genes. One lncRNA, called grumpy, was found to be a key regulator that promotes parasite differentiation into a quiescent, nondividing form that occurs once the parasite has reproduced to a critical density in host blood. In mouse experiments, the scientists found that overexpressing grumpy reduces parasitemia. "Grumpy's role in differentiation may be one example of a more general process used by the parasite to adapt to its environment," the study's authors write. "Understanding these regulatory processes may open up unexplored possibilities for developing therapeutic strategies to treat sleeping sickness."