Gene transcription is the first step that controls expression of the genetic information encoded in a genome and ultimately underlies cell differentiation and organism development. Eukaryotic gene transcription occurs in the context of highly structured and organised genomes and acts as a coordinator of numerous events co-occurring in the nucleus. Eukaryotic transcription relies on three different RNA polymerases: RNA polymerase I (Pol) transcribes ribosomal RNA, RNA Polymerase II synthesizes messenger RNAs and RNA polymerase III produces short and non-translated RNAs, including the entire pool of tRNAs, which are essential for cell growth.
For a long time, it was assumed that only Pol II was regulated whereas Pol I and Pol III, being devoted to house-keeping genes, did not require such control. However, it is now clear that RNA Polymerase III transcription is tightly regulated and a determinant of organismal growth. Pol III deregulation has been linked to cancer and genetic mutations causing severe neurodegenerative diseases.
Furthermore, Pol III (and its associated factors) play a paramount role into genome structure and organisation. These “extratranscriptional roles” are effected through interactions with transposon machineries, SMC complexes and specific chromatin remodellers.
The Vannini Group employs an Integrative Structural Biology approach, combining cutting-edge cryo-EM analysis, x-ray diffraction data, cross-linking and native mass-spectrometry. We integrate the structural data with molecular and cellular biology techniques in order to obtain a comprehensive view of these fundamental processes and how their mis-regulation leads to cancer and neurodegenerative diseases.
Vannini Group Pubilications
A micronutrient with major effects on cancer cell viability
Anastasia Kapara, Alessandro Vannini & Barrie Peck
2020 - Nature Metabolism
Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection
Ho JSY, Angel M, Ma Y, Sloan E, Wang G, Martinez-Romero C, Alenquer M, Roudko V, Chung L, Zheng S, Chang M, Fstkchyan Y, Clohisey S, Dinan AM, Gibbs J, Gifford R, Shen R, Gu Q, Irigoyen N, Campisi L, Huang C, Zhao N, Jones JD, van Knippenberg I, Zhu Z, Moshkina N, Meyer L, Noel J, Peralta Z, Rezelj V, Kaake R, Rosenberg B, Wang B, Wei J, Paessler S, Wise HM, Johnson J, Vannini A, Amorim MJ, Baillie JK, Miraldi ER, Benner C, Brierley I, Digard P, Łuksza M, Firth AE, Krogan N, Greenbaum BD, MacLeod MK, van Bakel H, Garcìa-Sastre A, Yewdell JW, Hutchinson E, Marazzi I.
2020 - Cell
DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability
Kramm K, Schröder T, Gouge J, Vera AM, Gupta K, Heiss FB, Liedl T, Engel C, Berger I, Vannini A, Tinnefeld P, Grohmann D.
2020 - Nature Communications
Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA
Muwen Kong, Erin E. Cutts, Dongqing Pan, Fabienne Beuron, Thangavelu Kaliyappan, Chaoyou Xue, Edward P. Morris, Andrea Musacchio, Alessandro Vannini, Eric C. Greene
2020 - Molecular Cell
TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation
Roberto Ferrari, Lara Isabel de Llobet Cucalon, Chiara Di Vona, Franc¸ ois Le Dilly, Enrique Vidal, Antonios Lioutas, Javier Quilez Oliete, Laura Jochem, Erin Cutts, Giorgio Dieci, Alessandro Vannini, Martin Teichmann, Susana de la Luna and Miguel Beato
2019 - Molecular Cell