Söderbom lab

The aim of our research is to understand the different functions of small RNAs – in the developing organism and as a defense system against pathogenic bacteria. Small RNAs are important regulators of most biological processes. These tiny 21 nt RNAs silence genes by guiding effector proteins to specific target (m)RNAs and thereby induce degradation, inhibit translation, or even turn off transcription. However, details of their underlying mechanisms are still obscure. In our research we use the amoeba Dictyostelium to study functions of small RNAs during growth and development. We also use Dictyostelium as a host model to explore small RNAs involvement in the infectious process when pathogenic bacteria, such as Mycobacteria, attack our cells.

Research

Small RNAs and their role in growth, development and infection

The main focus of our research is to understand how different biological processes are controlled by non-coding (nc)RNAs, with emphasis on gene regulation by small RNAs such as micro(mi)RNAs. For our studies we mainly use the genetically tractable social amoeba Dictyostelium discoideum, a unicellular organism that upon starvation enters a multicellular developmental program where cells differentiate and communicate.

NcRNAs are RNA molecules that are not translated. Instead, they have intrinsic functions, often executed by binding to complementary (m)RNA sequences to which they guide effector proteins. This can induce cleavage, DNA/RNA modifications, translational inhibition and much more. One class of ncRNAs is miRNAs, only ~21 nt long. These small RNAs bind to mRNAs and induce cleavage and/or translational inhibition and thereby down regulate gene expression. In humans miRNAs have been estimated to directly regulate about 60% of the genes, underscoring their importance.

One of our research aims is to better understand the biogenesis and function of miRNAs. Although miRNAs previously was believed to be unique to plants and animals, we and others have now shown that they are also present in some unicellular organisms, such as Dictyostelium. In order to study the function of miRNAs, we construct knock out strains of miRNA associated genes and investigate the effects on growth and development. We also use high throughput sequencing of small RNAs and mRNAs, of strains with different genetic backgrounds to nail down miRNA regulated target genes. In addition, we are interested in small RNAs involvement during infection by pathogenic bacteria, using Dictyostelium as a host model. Another project is to further reveal the function of an abundant class of ~50-90 nt long RNAs that previously discovered and that seem to play a role during early development in Dictyostelium.

Group members

Research leader: Fredrik Söderbom

Publications

Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity

Edelbroek, Bart; Kjellin, Jonas; Biryukova, Inna; Liao, Zhen et al.

Part of Nucleic Acids Research, p. 3121-3136, 2024
- DOI for Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity
- Download full text (pdf) of Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity
ProQ-dependent activation of Salmonella virulence genes mediated by post-transcriptional control of PhoP synthesis

Berggren, Sofia; Andresen, Liis; Kjellin, Jonas; Burgo, Yolanda Martinez et al.

Part of mSphere, 2024
- DOI for ProQ-dependent activation of Salmonella virulence genes mediated by post-transcriptional control of PhoP synthesis
- Download full text (pdf) of ProQ-dependent activation of Salmonella virulence genes mediated by post-transcriptional control of PhoP synthesis
Fractional 2 '-O-methylation in the ribosomal RNA of Dictyostelium discoideum supports ribosome heterogeneity in Amoebozoa

Diesend, Jan; Birkedal, Ulf; Kjellin, Jonas; Zhang, Jingwen et al.

Part of Scientific Reports, 2022
- DOI for Fractional 2 '-O-methylation in the ribosomal RNA of Dictyostelium discoideum supports ribosome heterogeneity in Amoebozoa
- Download full text (pdf) of Fractional 2 '-O-methylation in the ribosomal RNA of Dictyostelium discoideum supports ribosome heterogeneity in Amoebozoa
Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas

Kjellin, Jonas; Avesson, Lotta; Reimegård, Johan; Liao, Zhen et al.

Part of Genome Research, p. 436-447, 2021
- DOI for Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas
- Download full text (pdf) of Abundantly expressed class of noncoding RNAs conserved through the multicellular evolution of dictyostelid social amoebas
Saturation mutagenesis charts the functional landscape of Salmonella ProQ and reveals a gene regulatory function of its C-terminal domain

Rizvanovic, Alisa; Kjellin, Jonas; Söderbom, Fredrik; Holmqvist, Erik

Part of Nucleic Acids Research, p. 9992-10006, 2021
- DOI for Saturation mutagenesis charts the functional landscape of Salmonella ProQ and reveals a gene regulatory function of its C-terminal domain
- Download full text (pdf) of Saturation mutagenesis charts the functional landscape of Salmonella ProQ and reveals a gene regulatory function of its C-terminal domain
Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model

Kjellin, Jonas; Pränting, Maria; Bach, Frauke; Vaid, Roshan et al.

Part of BMC Genomics, 2019
- DOI for Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
- Download full text (pdf) of Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum

Liao, Zhen; Kjellin, Jonas; Höppner, Marc P.; Grabherr, Manfred et al.

Part of RNA Biology, p. 937-954, 2018
- DOI for Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum
- Download full text (pdf) of Global characterization of the Dicer-like protein DrnB roles in miRNA biogenesis in the social amoeba Dictyostelium discoideum
A host factor supports retrotransposition of the TRE5-A population in Dictyostelium cells by suppressing an Argonaute protein

Schmith, Anika; Spaller, Thomas; Gaube, Friedemann; Fransson, Asa et al.

Part of Mobile DNA, 2015
- DOI for A host factor supports retrotransposition of the TRE5-A population in Dictyostelium cells by suppressing an Argonaute protein
- Download full text (pdf) of A host factor supports retrotransposition of the TRE5-A population in Dictyostelium cells by suppressing an Argonaute protein
The Dictyostelium discoideum RNA-dependent RNA polymerase RrpC silences the centromeric retrotransposon DIRS-1 post-transcriptionally and is required for the spreading of RNA silencing signals

Wiegand, Stephan; Meier, Doreen; Seehafer, Carsten; Malicki, Marek et al.

Part of Nucleic Acids Research, p. 3330-3345, 2014
- DOI for The Dictyostelium discoideum RNA-dependent RNA polymerase RrpC silences the centromeric retrotransposon DIRS-1 post-transcriptionally and is required for the spreading of RNA silencing signals
A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum

Crona, Mikael; Avesson, Lotta; Sahlin, Margareta; Lundin, Daniel et al.

Part of Journal of Biological Chemistry, p. 8198-208, 2013
- DOI for A Rare Combination of Ribonucleotide Reductases in the Social Amoeba Dictyostelium discoideum
Evidence for Small RNAs Homologous to Effector-Encoding Genes and Transposable Elements in the Oomycete Phytophthora infestans

Vetukuri, Ramesh R.; Asman, Anna K. M.; Tellgren-Roth, Christian; Jahan, Sultana N. et al.

Part of PLOS ONE, 2012
- DOI for Evidence for Small RNAs Homologous to Effector-Encoding Genes and Transposable Elements in the Oomycete Phytophthora infestans
- Download full text (pdf) of Evidence for Small RNAs Homologous to Effector-Encoding Genes and Transposable Elements in the Oomycete Phytophthora infestans
MicroRNAs in Amoebozoa: Deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs

Avesson, Lotta; Reimegård, Johan; Wagner, Gerhart Eduard Heinrich; Söderbom, Fredrik

Part of RNA, p. 1771-1782, 2012
- DOI for MicroRNAs in Amoebozoa: Deep sequencing of the small RNA population in the social amoeba Dictyostelium discoideum reveals developmentally regulated microRNAs
Sequence and generation of mature ribosomal RNA transcripts in Dictyostelium discoideum

Boesler, Carsten; Kruse, Janis; Söderbom, Fredrik; Hammann, Christian

Part of Journal of Biological Chemistry, p. 17693-17703, 2011
- DOI for Sequence and generation of mature ribosomal RNA transcripts in Dictyostelium discoideum
Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease

Masson, Patrick; Lundin, Daniel; Söderbom, Fredrik; Young, Patrick

Part of Eukaryotic Cell, p. 844-851, 2009
- DOI for Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease
Dictyostelium discoideum salvages purine deoxyribonucleosides by highly specific bacterial-like deoxyribonucleoside kinases

Sandrini, Michael Paolo Bastner; Söderbom, Fredrik; Mikkelsen, Nils Egil; Piskur, Jure

Part of Journal of Molecular Biology, p. 653-664, 2007
- DOI for Dictyostelium discoideum salvages purine deoxyribonucleosides by highly specific bacterial-like deoxyribonucleoside kinases
Treasure hunt in an amoeba: non-coding RNAs in Dictyostelium discoideum.

Hinas, Andrea; Söderbom, Fredrik

Part of Current Genetics, p. 141-159, 2007
- DOI for Treasure hunt in an amoeba: non-coding RNAs in Dictyostelium discoideum.
HelF, a putative RNA helicase acts as a nuclear suppressor of RNAi but not antisense mediated gene silencing

Popova, Blagovesta; Kuhlmann, Markus; Hinas, Andrea; Söderbom, Fredrik et al.

Part of Nucleic Acids Research, p. 773-784, 2006
- DOI for HelF, a putative RNA helicase acts as a nuclear suppressor of RNAi but not antisense mediated gene silencing
RNase E cleavage in the 5' leader of a tRNA precursor.

Söderbom, Fredrik; Svärd, Staffan G; Kirsebom, Leif A

Part of J Mol Biol, p. 22-7, 2005
Requirements for the adenylyl cyclases in the development of Dictyostelium

Anjard, Christophe; Söderbom, Fredrik; Loomis, William F

Part of Development, p. 3649-3654, 2001
An adenylyl cyclase that functions during late development of Dictyostelium

Söderbom, Fredrik; Anjard, C; Iranfar, N; Fuller, D et al.

Part of Development, p. 5463-5471, 1999
SDF-2 induction of terminal differentiation in Dictyostelium discoideum is mediated by the membrane-spanning sensor kinase DhkA.

Wang, Nancy; Söderbom, Fredrik; Anjard, Christophe; Shaulsky, Gad et al.

Part of Molecular and Cellular Biology, p. 4750-4756, 1999
Cell-cell signaling during Dictyostelium development

Söderbom, Fredrik; Loomis, W F

Part of Trends in Microbiology, p. 402-406, 1998
- DOI for Cell-cell signaling during Dictyostelium development
PcnB is required for the rapid degradation of RNAI, the antisense RNA that controls the copy number of ColE1-related plasmids

He, Lin; Söderbom, Fredrik; Wagner, Gerhart; Binnie, Uta et al.

Part of Molecular Microbiology, p. 1131-1142, 1993
- DOI for PcnB is required for the rapid degradation of RNAI, the antisense RNA that controls the copy number of ColE1-related plasmids
Structural and functional analyses of the FinP antisense RNA regulatory system of the F conjugative plasmid

van Biesen, T; Söderbom, Fredrik; Wagner, E G; Frost, L S

Part of Molecular Microbiology, p. 35-43, 1993
- DOI for Structural and functional analyses of the FinP antisense RNA regulatory system of the F conjugative plasmid

People

Current group members

Fredrik Söderbom, PhD
Associate professor

Bart Edelbroek, PhD student

Rooma Mansoor, PhD student

Torgny Lundberg, Master student

Group alumni

Jonas Kjellin, former PhD student
Present: Uppsala Universitet, Sanna Koskiniemi group

Zhen Liao, former PhD student

Maria Pränting, former postdoc
Present: Information Officer at ReAct

Andrea Hinas, former PhD student

Åsa Fransson, former postdoc

Lotta Avesson, former PhD student

Anders Aspegren, former Post-doc

Roshan Vaid, former research assistant