The concept of miRNA clusters can be discussed on the basis of its transcriptional control and/or its genomic organization. Recently our group published a paper that could be interesting for you (Macedo C et al 2012 Immunobiology DOI: 10.1016./j.imbio.2012.06.013). As discussed in this paper, transcription factors (TFs) usually coordinately control a cluster of miRNA genes, which are initially transcribed into pri-miRNAs (Woods et al 2007 J Biol Chem vol 282: 2130). According to (Schmeier et al 2009 BMC Genomics vol 10: 595) the miRNAs that form these clusters tend to be regulated in a similar way. In our work published in Immunobiology, we show the same transcriptional profiling of a miRNA cluster encompassing the miRNA 376 family members and that spans about 23 kb on murine chromosome 12F1. These results show a link between genomic organization and transcriptional control of a miRNA cluster.

Hi,

maybe you'll find this paper informative:

Comparative genomic analysis reveals evolutionary characteristics and patterns of microRNA clusters in vertebrates.

Sun et al. 2012. Gene.

1st Question> difficult to answer with a rigorous definition. A microRNA cluster can be differently defined according to genomic data or transcriptomic data. "Next to each other", in miRBASE 19, means less than 10Kb, but i have analyzed several chip-seq database where i found that co-transcribed microRNAs can be more distant, but also that differentially transcribed microRNAs might be nearer...

microRNAs that are members of the same cluster are not alyways derived from the same ancestor.

The concept of miRNA clusters can be discussed on the basis of its transcriptional control and/or its genomic organization. Recently our group published a paper that could be interesting for you (Macedo C et al 2012 Immunobiology DOI: 10.1016./j.imbio.2012.06.013). As discussed in this paper, transcription factors (TFs) usually coordinately control a cluster of miRNA genes, which are initially transcribed into pri-miRNAs (Woods et al 2007 J Biol Chem vol 282: 2130). According to (Schmeier et al 2009 BMC Genomics vol 10: 595) the miRNAs that form these clusters tend to be regulated in a similar way. In our work published in Immunobiology, we show the same transcriptional profiling of a miRNA cluster encompassing the miRNA 376 family members and that spans about 23 kb on murine chromosome 12F1. These results show a link between genomic organization and transcriptional control of a miRNA cluster.

As rightly said by others, there is no certain criteria to define microRNA cluster. In some cases they do transcribe from the same ancestor but in many not. I am wondering does the "Seed sequence" has something to do with defining microRNAs in the same cluster?

I agree with Geraldo that clustered miRNAs can be regulated together by the same transcription factor but more and more papers show now that actually microRNA within one cluster are regulated differently by different transcription factors. In the region of my interest which is 14q there is a cluster of 8 microRNAs. In this particular case microRNA are differentially regulated by the same transcription factor and some of them require additional TFs to be transcribed. Moreover they do not derive from the same ancestor. Here are papers about that region: Song, 2008 PLOS ONE; Song 2008 Nucleic Acid Res; Davis, 2005 Curr Biol.

These papers may solve your query,

Comparative genomic analysis reveals evolutionary characteristics and patterns of microRNA clusters in vertebrates.

Identification of a two-layer regulatory network of proliferation-related microRNAs in hepatoma cells

ya its a cluster of 2 to 4 or many miRNAs. the details you can find here is some artical_

1) Molecular Evolution of a MicroRNA Cluster

doi:10.1016/j.jmb.2004.03.065

2) Clustering and conservation patterns of human miRNAs

doi:10.1093/nar/gki567

I think it may help you...........

In animals some mirnas belonging to a cluster may share the same sequence or seed , while others are totally different (see mir-17-92 cluster), so if they were the product of duplication events it must have happened very early during evolution. In plants mirnas belonging to a cluster usually have high sequence homology indicating that they are the products of duplication events .

It not more relevant that microRNAs are transcribed in the same primary miRNA in spite of they are not expressed in the same fashion than correlations in theirs expressions levels?

I thought that miRNA cluster refers to a set of miiRNAs which are close to each other in the genome , have the same promoter and are transcribed as a single primary transcript.

Yes Marcella, you're right. But the concept of miRNA cluster can also be discussed based on its transcriptional profile. Not only the genomic location, but if a group of miRNAs has a similar pattern of expression, they can be considered to be in the same cluster (would be an “expression cluster”). Therefore, it depends on the point of view. The important is to make clear what your point of view (what you are considering). I suggest to see my previous reply in this discussion.

But correlations in expressions levels can be casuals more than causals. We are working with let-7 cluster and, in spite of that miR-100, miR-125 and let-7 are transcribed in the same primary transcript, they show variations in expression profiles along time.

Yes Raúl, it shows that if we refer to a "miRNA expression cluster” we also have to make clear the model-system and the time point studied. It was good of you to remember that.

@Philippe Georgel, @Geraldo Passos, @Karolina Weiner-Gorzel, @Rakesh Sinha, @Girish Deokar Thanks all of you for providing useful papers;

@Matteo Marzi You mentioned distant microRNAs can be co-transcribed? You mean these microRNAs are from a single primary miRNA, or have same expression profile, which, I think,does not require them to be transcribed from the same primary miRNA? And as @Raúl Montañez Martínez mentioned even microRNAs are transcribed from the same primary miRNA, they show variations in expression profile. So, @Raúl Montañez Martínez and @Matteo Marzi, what is the most direct way to examine whether adjacent microRNAs are transcribed from a primary miRNA?

@Eyal Mor Does How to check wether these miRNAs share the same ancestor? Any recommended detailed method?

We want to demonstrate 4 microRNAs in a cluster have distinct function. Any suggestions?

All of them are in plants

http://www.ncbi.nlm.nih.gov/pubmed/16040653

http://www.ncbi.nlm.nih.gov/pubmed/16888323

http://www.ncbi.nlm.nih.gov/pubmed/19304749

I can only recommend to align the miRNAs sequences to see if they are similar. This would indicate a common ancetor. If they are not but one of them is similar to another miRNA (for example, another member of the same miRNA family), this might indicate that it was duplicated from that sequence.

Usually miRNA cluster is defined as miRNAs positioned closer than a given distance (Altuvia ey al 2005), but sometimes miRNAs are coexpressed up to 50 knt. Statistical size of miRNA cluster (i.e. maximal size of typical cluster) can be revealed by analyzing their intragenomic positional correlations: for human it is about 5 knt (Titov and Vorozheykin (2011) Analysis of miRNA Duplication in the Human Genome and the Role of Transposon Evolution in This Process. Russian Journal of Genetics: Applied Research V.1 N 4 pp 307-313)

It is difficult to define the physical boundaries for "clusters"; If miRNAs with same/similar mature miRNA are present in tandem in a cluster they are likely to have evolved through local tandem duplication and thus are paralogs; however one such tandemly duplicated block may further be duplicated at another part of the genome. The ancestral relationship between miRNAs in the second block is thus not the same as was in the first block. I suggest that you can align the precursors of the miRNA to gain insight into their evolutionary relationship. (http://link.springer.com/article/10.1007/s11816-011-0208-x)