Department of RNA Metabolism


Head:
Zbigniew Warkocki, PhD

 

 

 


Staff:
Karolina Drążkowska, PhD

Katarzyna Chojnacka, MSc;

Martyna Kordyś, MSc


 

PhD Students:

Dmytro Pandakov, Msc

 


 
 

 


 

 

 

 

 

 

 

 

 

 

Keywords:

RNA metabolism, posttranscriptional regulation of gene expression, RNA uridylation, polyadenylation, human retrotransposons LINE-1 and Alu, TAIL-seq, 3’ RACE-seq, protein and RNA co-IP and proteomics


Research area

The Department of RNA Metabolism was established in May 2018.

Our research concentrates on investigation of RNA and natural mechanisms of its metabolism in human cells.

 

Research topic #1

  • Molecular mechanisms of RNA 3’ uridylation

 

Uridylation is a process of addition of non-templated uridine residues to RNA 3’ ends. Uridylation plays important roles in early development and pluripotent cells thus research in the Department utilizes pluripotent human and murine cellular models.

 

Research topic #2

  • Post-transcriptional regulation of human retrotransposons LINE-1 and ALU

 

Nearly half of the human genome is occupied by repetitive elements including retrotransposons: LINE-1 and ALU. Retrotransposons propagate by a copy-and-paste mechanism involving RNA intermediates. LINE-1 and ALU activity might lead to de novo insertions in gametes and developing embryos. Furthermore, an increasing amount of experimental evidence points to important roles of LINE-1 and ALUs in perpetuating human autoimmune disorders, cellular senescence and ageing. In the Department molecular mechanisms of LINE-1 and ALU regulation at post-transcriptional levels are addressed.

 

Ongoing research projects

1. Mechanisms of human gene expression regulation by uridylation

NCN SONATA-13 (UMO-2017/26/D/NZ1/00887)

 

2. Degradation pathways of transcripts associated with human diseases the basis of which is the expansion of microsatellite sequences

NCN FUGA

 

3. Mechanisms of LINE-1 in an autoimmune disorder – preliminary studies

MNiSW grant for young scientists

 

4. International collaboration with Dr Jose L. Garcia-Perez Institute of Genetics and Molecular   Medicine, Edinburgh, UK

EMBO STF

 

Publications

1. Kobyłecki K, Drążkowska K, Kuliński TM, Dziembowski A, Tomecki R.
Elimination of 01/A'-A0 pre-rRNA processing by-product in human cells involves cooperative action of two nuclear exosome-associated nucleases: RRP6 and DIS3.
RNA. 2018 Dec;24(12):1677-1692. doi: 10.1261/rna.066589.118. PMID:30266864

2. Warkocki Z, Liudkovska V, Gewartowska O, Mroczek S, Dziembowski A.
Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism.
Philos Trans R Soc Lond B Biol Sci. 2018 Nov 5;373(1762). doi: 10.1098/rstb.2018.0162. PMID:30397099

3. Warkocki, Z., Krawczyk, PS., Adamska, D., Bijata, K., Garcia-Perez, JL., Dziembowski, A. Uridylation by TUT4/7 restricts retrotransposition of human LINE-1s.
Cell 2018 Sep 6;174(6):1537-1548.e29. https://doi.org/10.1016/j.cell.2018.07.022 (2018)

4. Razew, M., Warkocki, Z., Taube, M., Kolondra, A., Czarnocki-Cieciura, M., Nowak, E., Labedzka-Dmoch, K., Kawinska, A., Piatkowski, J., Golik, P., et al.
Structural analysis of mtEXO mitochondrial RNA degradosome reveals tight coupling of nuclease and helicase components.
Nature Communications 9, 97. PMID: 29311576 (2018)

5. Szczesny, R.J., Kowalska, K., Klosowska-Kosicka, K., Chlebowski, A., Owczarek, E.P., Warkocki, Z., Kulinski, T.M., Adamska, D., Affek, K., Jedroszkowiak, A., et al.
Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system.
PLoS ONE 13, e0194887 PMID: 29590189 (2018).

6. Łabno, A., Warkocki, Z., Kuliński, T., Krawczyk, P.S., Bijata, K., Tomecki, R., and Dziembowski, A.
Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs.
Nucleic Acids Research 44, 10437–10453. PMID: 27431325 (2016).

7. Warkocki, Z., Schneider, C., Mozaffari-Jovin, S., Schmitzová, J., Höbartner, C., Fabrizio, P., and Lührmann, R.
The G-patch protein Spp2 couples the spliceosome-stimulated ATPase activity of the DEAH-box protein Prp2 to catalytic activation of the spliceosome.
Genes & Development 29, 94–107. PMID: 25561498 (2015)