Nucleomodulins are a family of bacterial proteins that enter the nucleus of eukaryotic cells. This term comes from the contraction between "nucleus" and "modulins", which are microbial molecules that modulate the behaviour of eukaryotic cells. Nucleomodulins are produced by pathogenic or symbiotic bacteria. They act on various processes in the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

: remodelling of the chromatin structure,

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

, splicing of pre-messenger RNA, cell division. The identification of nucleomodulins in several species of bacterial pathogens of humans, animals and plants has led to the emergence of the concept that direct control of the nucleus is one of the most sophisticated strategies used by microbes to bypass host defences. Nucleomodulins can be directly secreted into the intracellular medium after entry of the bacteria into the cell, like '' Listeria monocytogenes'', or they can be injected from the extracellular medium or intracellular

organelle In cell biology, an organelle is a specialized subunit, usually within a cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as organs are to the body, hence ''organelle,'' the ...

s using a type

III III or iii may refer to: Companies * Information International, Inc., a computer technology company * Innovative Interfaces, Inc., a library-software company * 3i, formerly Investors in Industry, a British investment company Other uses * Ins ...

or IV bacterial secretion system, also known as a "molecular syringe". More recently, it has been shown that some of them, such as YopM from '' Yersinia pestis'' and IpaH9.8 from ''

Shigella flexneri ''Shigella flexneri'' is a species of Gram-negative bacteria in the genus ''Shigella'' that can cause diarrhea in humans. Several different serogroups of ''Shigella'' are described; ''S. flexneri'' belongs to group ''B''. ''S. flexneri'' infecti ...

'', can autonomously penetrate eukaryotic cells thanks to a membrane transduction domain. The diversity of molecular mechanisms triggered by nucleomodulins is a source of inspiration for new biotechnologies. They are true nano-machines capable of hijacking a multitude of nuclear processes. In research, nucleomodulins are the subject of in-depth studies that have led to the discovery of new human nuclear regulators, such as the

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

regulator BAHD1.

Examples

Agrobacterium tumefaciens ''Agrobacterium radiobacter'' (more commonly known as ''Agrobacterium tumefaciens'') is the causal agent of crown gall disease (the formation of tumours) in over 140 species of eudicots. It is a rod-shaped, Gram-negative soil bacterium. Sympto ...

'', responsible for crown gall disease, produces an arsenal of Vir proteins, including VirD2 and VirE2, enabling the precise integration of a piece of its DNA, called

T-DNA The transfer DNA (abbreviated T-DNA) is the transferred DNA of the tumor-inducing (Ti) plasmid of some species of bacteria such as ''Agrobacterium tumefaciens'' and ''Agrobacterium rhizogenes(actually an Ri plasmid)''. The T-DNA is transferred fr ...

, into that of the host plant '' Listeria monocytogenes'', responsible for listeriosis, can modulate the expression of immunity genes. One of the mechanisms at play involves the bacterial protein LntA, which inhibits the function of the epigenetic regulator BAHD1. The action of this nucleomodulin is associated with chromatin decompaction and activation of an interferon response genes. ''

'', responsible for shigellosis, secretes the IpaH9.8 protein targeting a mRNA splicing protein that disrupts the production of protein isoforms and the inflammatory response in humans.

Legionella pneumophila ''Legionella pneumophila'' is a thin, aerobic, pleomorphic, flagellated, non-spore-forming, Gram-negative bacterium of the genus ''Legionella''. ''L. pneumophila'' is the primary human pathogenic bacterium in this group and is the causative age ...

, responsible for legionellosis, secretes an enzyme with histone methyltransferase activity capable of methylating histones at different chromosome loci or at the level of ribosomal DNA (rDNA) in the nucleolus.{{Cite journal, last1=Li, first1=Ting, last2=Lu, first2=Qiuhe, last3=Wang, first3=Guolun, last4=Xu, first4=Hao, last5=Huang, first5=Huanwei, last6=Cai, first6=Tao, last7=Kan, first7=Biao, last8=Ge, first8=Jianning, last9=Shao, first9=Feng, display-authors=1, date=August 2013, title=SET‐domain bacterial effectors target heterochromatin protein 1 to activate host rDNA transcription, journal=EMBO Reports, language=en, volume=14, issue=8, pages=733–740, doi=10.1038/embor.2013.86, issn=1469-221X, pmc=3736128, pmid=23797873

References

Genetics