Discovery and seminal developments in the CRISPR field

TY - CHAP

T1 - Discovery and seminal developments in the CRISPR field

AU - Mojica, Francisco J.M.

AU - Garrett, Roger Antony

PY - 2013/1/1

Y1 - 2013/1/1

N2 - In the late 1980s and early 1990s, arrays of regularly spaced repeats were detected in both bacterial and archaeal genomes. They are currently known as Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR. Advances in our understanding of their biological significance and potential applications for biotechnology have followed a two-phased development. Initial studies were few and mainly descriptive of arrays of interspaced repeats in bacteria and archaea and of physically linked conserved genes that were inferred to be cofunctional. Moreover, before their function was revealed, repeat-spacer arrays of Mycobacterium spp were employed as novel markers for bacterial genotyping. The second phase began in 2005, with the discovery of a link between CRISPR arrays and host protection against invading genetic elements. This finding fuelled a plethora of biochemical and genetic studies directed at characterising the mechanistic details of this novel and complex genetic barrier. First, this led to the finding that the repeats, spacers, CRISPR-associated (Cas) proteins and partially conserved leader regions flanking one end of the CRISPR array, constitute the essential functional components. Subsequently, three primary functional steps were defined: (1) acquisition (also termed adaptation): uptake of new spacers at or near the leader sequence, (2) expression: generation of CRISPR transcripts from within the leader region and their processing into small mature CRISPR RNAs (crRNAs) carrying all or most of the spacer sequence and (3) interference: involving protein-crRNA complexes targeting and cleaving foreign genetic elements. Only now can we begin to comprehend the complex functional interactions and diversity of CRISPR-based systems, and the implications of their adaptive nature. Here, we describe the early developments in the CRISPR field and relate them to our current understanding of how these novel, complex and diverse systems function.

AB - In the late 1980s and early 1990s, arrays of regularly spaced repeats were detected in both bacterial and archaeal genomes. They are currently known as Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR. Advances in our understanding of their biological significance and potential applications for biotechnology have followed a two-phased development. Initial studies were few and mainly descriptive of arrays of interspaced repeats in bacteria and archaea and of physically linked conserved genes that were inferred to be cofunctional. Moreover, before their function was revealed, repeat-spacer arrays of Mycobacterium spp were employed as novel markers for bacterial genotyping. The second phase began in 2005, with the discovery of a link between CRISPR arrays and host protection against invading genetic elements. This finding fuelled a plethora of biochemical and genetic studies directed at characterising the mechanistic details of this novel and complex genetic barrier. First, this led to the finding that the repeats, spacers, CRISPR-associated (Cas) proteins and partially conserved leader regions flanking one end of the CRISPR array, constitute the essential functional components. Subsequently, three primary functional steps were defined: (1) acquisition (also termed adaptation): uptake of new spacers at or near the leader sequence, (2) expression: generation of CRISPR transcripts from within the leader region and their processing into small mature CRISPR RNAs (crRNAs) carrying all or most of the spacer sequence and (3) interference: involving protein-crRNA complexes targeting and cleaving foreign genetic elements. Only now can we begin to comprehend the complex functional interactions and diversity of CRISPR-based systems, and the implications of their adaptive nature. Here, we describe the early developments in the CRISPR field and relate them to our current understanding of how these novel, complex and diverse systems function.

U2 - 10.1007/978-3-642-34657-6_1

DO - 10.1007/978-3-642-34657-6_1

M3 - Book chapter

SN - 978-3-642-34656-9

SP - 1

EP - 31

BT - CRISPR-Cas Systems

A2 - Barrangou, Rodolphe

A2 - van der Oost, John

PB - Springer VS

ER -