Regulation of genome expression is essential for cell proliferation, differentiation, development and viability. Small RNA silencing pathways are involved in the cellular control of gene expression and in protection of the genome against mobile repetitive DNA sequences, retroelements and transposons. Small RNAs interact with target RNAs and promote chromatin modifications, translational inhibition or degradation of complementary RNAs. We have uncovered new class of small RNAs in fission yeast, priRNAs, which are generated independently of Dicer. We propose that priRNAs are involved in triggering of siRNA amplification and heterochromatin assembly within centromeric repeats. As a part Biosys network we will combine small RNA sequencing and transcriptomic approaches with with biochemistry and functional assays to determine biogenesis and function of Dicer-independent priRNAs. priRNA biogenesis in fission yeast is likely to resemble biogenesis of piRNAs and other Dicer-independent small RNAs in higher eukayotes. Furthermore, we will test our hypothesis that priRNAs are used in genome surveillance to recognize elements which should be targeted by RNAi. In addition to small RNAs, we will study which other factors determine recruitment of RNAi to specific genes. Defects in small RNA-mediated regulation of genome expression have been described in several human cancers. Fundamental understanding of the role of small RNAs in gene regulation will help us understand why some cells loose their identity and turn into cancer cells

Mirela Marasovic

Manuel Zocco

Marasovic M, Zocco M, Halic M (2013). Argonaute and Triman generate dicer-independent priRNAs and mature siRNAs to initiate heterochromatin formation. Mol Cell 52(2):173-83. 

Gerace E, Halic M, Moazed D

The Methyltransferase Activity of Clr4Suv39h triggers RNAi Independently of Histone H3K9 Methylation.

Mol Cell. 2010 Aug 13;39(3):360-72.

Halic M and Moazed D

Dicer-Independent priRNAs and Argonaute Trigger RNAi and Heterochromatin Formation

Cell. 2010 Feb 19;140(4):504-516

Bhushan S, Gartmann M, Halic M, Armache JP, Jarasch A, Mielke T, Berninghausen O, Wilson DN, Beckmann R

α-Helical nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel

Nat Struct Mol Biol. 2010; Published online: 7 February 2010 | doi:10.1038/nsmb.1756

Halic M, Moazed D.

22G-RNAs in transposon silencing and centromere function.

Mol Cell. 2009 Oct 23;36(2):170-1.

Halic M, Moazed D.

Transposon silencing by piRNAs.

Cell. 2009 Sep 18;138(6):1058-60

Halic M, Blau M, Becker T, Mielke T, Pool MR, Wild K, Sinning I, Beckmann R

Following the Signal Sequence from the Ribosomal Tunnel Exit to Signal Recognition Particle

Nature. 2006 Nov 23;444(7118):507-11.

Andersen CB, Becker T, Blau M, Anand M, Halic M, Balar B, Mielke T, Boesen T, Pedersen JS, Spahn CM, Kinzy TG, Andersen GR, Beckmann R.

Structure of eEF3 and the mechanism of transfer RNA release from the E-site.

Nature. 2006 Oct 12;443(7112):663-8.

Halic M, Gartmann M, Schlenker O, Mielke T, Pool MR, Sinning I, Beckmann R

Signal recognition particle receptor exposes the ribosomal translocon binding site.

Science. 2006 May 5;312(5774):745-7.

Halic M, Becker T, Frank J, Spahn CM, Beckmann R.

Localization and dynamic behavior of ribosomal protein L30e.

Nat Struct Mol Biol. 2005 May;12(5):467-8. Epub 2005 May 1.

Halic M, Beckmann R.

The signal recognition particle and its interactions during protein targeting.

Curr Opin Struct Biol. 2005 Feb;15(1):116-25. Review.

Halic M, Becker T, Pool MR, Spahn CM, Grassucci RA, Frank J, Beckmann R.

Structure of the signal recognition particle interacting with the elongation-arrested ribosome.

Nature. 2004 Feb 26;427(6977):808-14.

Wild K*, Halic M*, Sinning I, Beckmann R.

SRP meets the ribosome.

Nat Struct Mol Biol. 2004 Nov;11(11):1049-53. Review. * Both authors contributed equally